Evaluation of the Potential Protectivity of Both Allium sativum and Zingiber officinale on the Cadmium-Induced Testicular Damage in Rats.

Background: Cadmium (Cd) is a widely spread environmental pollutant, listed among the unsafe metals due to known toxic effects on multiple organs, including the testes. In this study, we aim to evaluate the potential protectivity of garlic and ginger extracts on Cd-induced damage of the testis in rats. Materials and Methods: Fifty-six adult male albino rats were alienated into seven groups; control group, garlic-treated group, and ginger-treated group were given garlic and ginger extracts at doses of 250 mg and 120 mg/kg b.wt/day, Cd-treated group received 8.8 mg/Kg b.wt/day of Cd chloride, and the protected groups were given Cd and co-treated with garlic, ginger, or both extracts. The testes were subjected to different procedures to assess the oxidative status and histopathological changes. Results: Cd-treated rats showed a significant reduction in the testis weight and morphometric measurements of the seminiferous tubules compared to the control group. Cd administration resulted in a marked drop in the testosterone level and activities of antioxidative enzymes. Moreover, Cd induced histopathological changes in the seminiferous tubules. Co-administration of garlic and ginger extracts with the Cd showed partial improvement in the investigated parameters toward the control figures and improvement in the morphological changes. Co-treating both extracts together and the Cd resulted in complete normalization of these adverse effects of Cd. Conclusion: These findings indicated that garlic and ginger extracts could ameliorate the harmful effects of Cd on the testis. This effect was more prominent when garlic and ginger extracts were co-administered together with Cd.

UHPLC-MS/MS profiling and in vivo aphrodisiac and androgenic effects of the aqueous extract of the roots of Schumanniophyton magnificum (K. Schum.) Harms.

ETHNOPHARMACOLOGICAL RELEVANCE: Schumanniophyton magnificum is a medicinal plant used to manage many ailments including malaria, skin diseases, parasitic infections, male sexual dysfunctions, female infertility and typhoid fever. However, no scientific investigation has been made for its folkloric use by the "Baka" Pygmies of Cameroon as an aphrodisiac. AIM OF THE STUDY: To investigate the aphrodisiac and androgenic activities of the aqueous extract of the roots of Schumanniophyton magnificum in male rats and analyze the phytoconstituents by UHPLC/MS. MATERIALS AND METHODS: Twenty-five male rats of 16-weeks old were divided into 5 groups and orally treated for 30 days with distilled water (10 ml/kg), or sildenafil citrate (5 mg/kg), or the aqueous extract of Schumanniophyton magnificum (43 mg/kg, 86 mg/kg and 172 mg/kg). The sexual behaviour parameters were monitored on day 1 and 30 by pairing male rats to receptive females. At the end of the experiment, rats were killed and the blood and reproductive organs were collected for histological sectioning, sperm analysis and biochemical analysis. The presence of phytoconstituents and their structures were revealed by UHPLC/MS. RESULTS: The plant extract significantly increased the mount, ejaculation and intromission frequencies in comparison to those in the normal control group; and significantly doubled the serum testosterone levels (2.15 ± 0.70 ng/ml) compared to the normal control group. UHPLC/MS of the aqueous extract of Schumanniophyton magnificum identified 7 major compounds such as Schumanniofioside A, Noreugenin and Rohitukine, with antioxidant and antibacterial activities. The plant extracts significantly increased the penile nitric oxide levels (P ˂0.05). These results were similar to those obtained after administration of sildenafil citrate. CONCLUSIONS: The aqueous extract of Schumanniophyton magnificum could be an alternative for erectile dysfunction management.

The Role of Phthalocyanine-Gold Nanoconjugates (Pc-Au NCs) in Ameliorating the Hepatic and Renal Toxicity-Induced by Silver Nanoparticles (Ag NPs) in Male Rats.

Recently, gold nanoparticles (Au Nps) have gained tremendous attention for its unique properties as a safe nanocarrier for delivering drugs that are used in different disease diagnoses. Although silver nanoparticles (Ag NPs) have been generally applied due to their strong antibacterial, antiviral, antifungal, and antimicrobial properties, their toxicity is a subject of sustained debate, thus requiring further studies. The present study aims to evaluate the potential protective effect of gold nanoparticles and phthalocyanine-gold nanoconjugates (Pc-Au NCs) against the hepatorenal toxicity of silver nanoparticles in male rats. Herein, 60 adult male Rattus norvegicus rats were divided into six equal groups (n = 10/group); the first group was kept as control, the second received gold nanoparticles (Au NPs) intraperitoneally (10 µg/kg) daily for 3 weeks, the third group is gold-phthalocyanine (Pc-Au) group where rats were injected intraperitoneally with gold-phthalocyanine for 3 weeks (10 µg/kg), the fourth group received silver nanoparticles (Ag NPs) (4 mg/kg) daily intraperitoneally for 3 weeks, the fifth group is silver + gold nanoparticles group (Ag + Au), and the sixth is silver + gold-phthalocyanine nanoconjugates (Ag + Pc-Au) group in which rats were intraperitoneally injected firstly with Ag NPs (4 mg/kg) for 3 weeks then with gold or gold-phthalocyanine for another 3 weeks (10 µg/kg). Our results revealed that Ag NPs could increase the serum AST, ALT, ALP, urea, creatinine, and lipid profile and significantly decreased the total protein and albumin. Moreover, histopathological alterations detected in the kidney and the liver of the Ag NPs group included vascular congestion, inflammatory cell infiltration, and tissue distortion. Alongside, exposure to Ag NPs induces hepatic and renal oxidative stress by suppressing the antioxidant-related genes including glutathione peroxidase 1 (gpx1), superoxide dismutase (sod), and catalase (cat). Ag NPs also upregulated the hepatic and renal genes involved in inflammation such as the interleukin-6 (il-6) and tumor necrosis factor-α (tnf-α), nuclear factor kappa B (nf-κß), apoptosis such as the BCL2 associated X (bax), casp3, and other related to metabolism including asparagine synthetase (asns), suppressor of cytokine signaling 3 (socs3), MYC proto-oncogene (myc), and C-C motif chemokine ligand 2 (ccl2). On the other hand, treatment with Au NPs and Pc-Au NCs could effectively ameliorate the hepatorenal damages induced by Ag NPs and improve liver and kidney architecture and function, especially in the Pc-Au NCs group. Briefly, our study revealed the underlined mechanism of Ag NPs hepatotoxic and nephrotoxic effects and that Pc-Au NCs could alleviate these adverse impacts via their anti-oxidative, anti-apoptotic, and anti-inflammatory activities.

Effects of acute carbon monoxide poisoning on liver damage and comparisons of related oxygen therapies in a rat model.

Acute carbon monoxide (CO) poisoning may cause liver damage and liver dysfunction. Therefore, in this study, we aimed to compare the efficiency of normobaric oxygen (NBO) and high-flow nasal cannula oxygen (HFNCO) treatments on liver injury. For that purpose, 28 male Wistar albino rats were divided into four groups (Control, CO, CO + NBO, and CO + HFNCO). The control group was allowed to breath room air for 30 min. Acute CO poisoning in CO, CO + NBO, CO + HFNCO was induced by CO exposure for 30 min. Thereafter, NBO group received 100% NBO with reservoir mask for 30 min. HFNCO group received high-flow oxygen through nasal cannula for 30 min. At the end of the experiment, all animals were sacrificed by cardiac puncture under anesthesia. Serum liver function tests were measured. Liver tissue total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels, tissue histomorphology and immunoexpression levels of Bax, Caspase 3, TNF-α, IL-1ß, and NF-κB were also examined. Our observations indicated that acute CO poisoning caused significant increases in blood COHb, serum aminotransferase (AST), alanine aminotransferase (ALT0, alkaline phosphatase (ALP), total protein, albumin, and globulin levels but a decrease in albumin to globulin ratio (all, p < 0.05). Furthermore, acute CO poisoning significantly increased the OSI value, and the immunoexpresssion of Bax, Caspase 3, TNF-α, IL-1ß, and NF-κB in liver tissue (all, p < 0.05). These pathological changes in serum and liver tissue were alleviated through both of the treatment methods. In conclusion, both the NBO and HFNCO treatments were beneficial to alleviate the acute CO poisoning associated with liver injury and dysfunction.

Propionic acid affects the synaptic architecture of rat hippocampus and prefrontal cortex.

It is well documented that propionic acid (PPA) produces behavioral, morphological, molecular and immune responses in rats that are characteristic of autism spectrum disorder in humans. However, whether PPA affects the ultrastructure and synaptic architecture of regions of autistic brain has not been adequately addressed. Earlier we show that single intraperitoneal (IP) injection of PPA (175 mg/kg) produces superficial changes in the spatial memory and learning of adolescent male Wistar rats. However, in neurons, synapses and glial cells of hippocampal CA1 area and medial prefrontal cortex transient (mainly) or enduring alterations were detected. In this study, we used electron microscopic morphometric analysis to test the effect of PPA on different structural parameters of axodendritic synapses of the hippocampus and prefrontal cortex. The animals were treated with a single IP injection of PPA (175 mg/kg). The length and width of synaptic active zone, the area of presynaptic and postsynaptic mitochondria, the distance between presynaptic mitochondria and the synapse active zone, the distance between postsynaptic mitochondria and postsynaptic density and the depth and opening diameter of neuronal porosome complex were evaluated. Our results show that synaptic mitochondria of the hippocampus and prefrontal cortex are the most vulnerable to PPA treatment: in both regions, the area of postsynaptic mitochondria were increased. In general, our results show that even small dose of PPA, which produces only superficial effects on spatial memory and learning is able to alter the synapse architecture in brain regions involved in cognition and autism pathogenesis. Therefore, the microbiome may be involved in the control of neurotransmission in these regions.

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress.

Any deviation from the programmed processes of brain development may modify its formation and functions, thereby precipitating pathological conditions, which often become manifest in adulthood. Exposure to a challenge during crucial periods of vulnerability, such as adolescence, may reveal molecular changes preceding behavioral outcomes. Based on a previous study showing that prenatal fluoxetine (FLX) leads to the development of an anhedonic-like behavior in adult rats, we aimed to assess whether the same treatment regimen (i.e., fluoxetine during gestation; 15 mg/kg/day) influences the ability to respond to acute restraint stress (ARS) during adolescence. We subjected the rats to a battery of behavioral tests evaluating the development of various phenotypes (cognitive deficit, anhedonia, and anxiety). Furthermore, we carried out molecular analyses in the plasma and prefrontal cortex, a brain region involved in stress response, and whose functions are commonly altered in neuropsychiatric conditions. Our findings confirm that prenatal manipulation did not affect behavior in adolescent rats but impaired the capability to respond properly to ARS. Indeed, we observed changes in several molecular key players of the hypothalamic pituitary adrenal axis, particularly influencing genomic effects mediated by the glucocorticoid receptor. This study highlights that prenatal FLX exposure influences the ability of adolescent male rats to respond to an acute challenge, thereby altering the functionality of the hypothalamic-pituitary-adrenal axis, and indicates that the prenatal manipulation may prime the response to challenging events during this critical period of life.

Parental Social Isolation during Adolescence Alters Gut Microbiome in Rat Male Offspring.

Previous work from our laboratory demonstrated that parental stress, induced by social isolation starting at puberty, leads to behavioral, endocrine, and biochemical changes in the male, but not female, offspring (ISO-O) of Sprague-Dawley rats. Here, we report alterations in the gut microbiota composition of ISO-O vs. grouped-housed offspring (GH-O), although all animals received the same diet and were housed in the same conditions. Analysis of bacterial communities by next-generation sequencing (NGS) of 16S rRNA gene revealed alterations at family and order levels within the main phyla of Bacteroides, Proteobacteria, and Firmicutes, including an almost total deficit in Limosilactobacillus reuteri (formerly Lactobacillus reuteri) and a significant increase in Ligilactobacillus murinus (formerly Lactobacillus murinus). In addition, we found an increase in the relative abundance of Rhodospirillales and Clostridiales in the families of Lachnospiraceae and Ruminococcaceae, and Bacteroidales in the family of Prevotellaceae. Furthermore, we examined plasma levels of the proinflammatory cytokines interleukin-1-beta and tumor necrosis factor-alpha, which did not differ between the two groups, while corticosterone concentrations were significantly increased in ISO-O rats. Our findings suggest that adverse environmental conditions experienced by parents may have an impact on the likelihood of disease development in the subsequent generations.

Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. In this report, we explored mGluR2/3 expression following blast exposure in male rats. Western blotting revealed that mGluR2 protein (but not mGluR3) was increased in all brain regions studied (anterior cortex, hippocampus, and amygdala) at 43 or 52 weeks after blast exposure but not at 2 weeks or 6 weeks. mGluR2 RNA was elevated at 52 weeks while mGluR3 was not. Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury.

The Role of Chlorella vulgaris in Attenuating Infertility Induced by Cadmium Chloride via Suppressing Oxidative Stress and Modulating Spermatogenesis and Steroidogenesis in Male Rats.

Cadmium (Cd) is an environmental pollutant known as endocrine disruptor . Cd has been reported to induce perturbations of the testicular functions and the subsequent decline of the male fertility of both animals and humans. Chlorella vulgaris (ChV) a species of green microalga has been reported to have multiple beneficial activities such as anti-inflammatory, antioxidant, and antiapoptotic effects. Thus, this work was conducted to declare the benefits of Chlorella vulgaris (ChV) (500 mg/kg doses) against cadmium chloride CdCl2 (2 mg/kg doses) toxicity on the main and accessory reproductive organs' weight, structure, and function of male rats. Briefly, 40 adult male rats in 4 groups (n = 10) were used as follows; control, ChV, CdCl2, and CdCl2+ChV. (i) The 1st group was kept as control fed on pellet chow and water ad libitum. (ii) The second group is Chlorella vulgaris (ChV) group fed with C. vulgaris alga for 10 days (500 mg/kg BW). (iii) The third group was administrated CdCl2 (2mg/kg BW) via subcutaneous injection (S/C) daily for 10 days. (iv) The fourth group administered both CdCl2 and ChV with the abovementioned doses daily for successive 10 days. Our observations declared that cadmium exhibited an adverse influence on the testes and prostate gland architecture indicated by seminiferous tubule destruction, testicular edema, degeneration of Leydig cells, and prostate acini damage. All together affect the epididymal semen quality and quantity including sperm viability, motility, and count. Interestingly, ChV could restore the testicular architecture and spermatozoa regeneration accompanied by semen quality improvement and increased reproductive hormones including testosterone. On the other side, ChV suppresses reactive oxygen species (ROS) formation via enhancement the antioxidant-related genes in the testicular tissue including SOD, CAT, GSH, and MDA and maintaining spermatocyte survival via suppression of apoptotic related genes including caspase3 and activating steroidogenic related genes including StAR and HSD17ß3 in the cadmium-treated testes. In this study, ChV could enhance male fertility under normal or stressful conditions and ameliorate the adverse effects of hazardous heavy metals that are widely distributed in our environment.

Assessment of Ante- and Postnatal Development of the Offspring of Male Rats Crossed in Delayed Periods after Treatment with Methotrexate in Low Doses.

We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.

The antioxidant/anti-inflammatory protective effects of rutin against ethanol-induced testicular perturbation in rats: Involvement of the immunosuppressive indoleamine 2,3-dioxygenase.

This study investigated the influence of rutin against EtOH-induced testicular impairment in rats and the involvement of the indole-aminergic pathway. Four groups of eight rats each were orally exposed to drinking water (Group 1), EtOH (5 g/kg bwt, Group 2), R (5 g/kg bwt, Group 3), and EtOH + R (5 g/kg bwt + 50 mg/kg bwt, Group 4) via gavage for 15 days. Results showed that exposure to EtOH significantly (p < 0.0001) reduced the testicular antioxidant system and increased lipid peroxidation (LPO) relative to control. We observed a significant (p < 0.0001) increase in the inflammatory biomarkers, with attendant disruption in the testicular histological structure and concomitant elevation in the activities of indoleamine 2,3-dioxygenase (IDO), in comparison with control and no noticeable effects in tryptophan 2,3-dioxygenase (TDO) activity across the groups. Rutin-only exposed group did not show any alteration in the measured parameters when compared with the control. Rutin co-exposure augmented the antioxidant system, prevented histological damage, reduced LPO and inflammation, and thus, lowered EtOH-mediated increase in IDO activity, compared with control. Overall, these findings reveal the involvement of the indole-aminergic pathway in rutin's protective influence against EtOH-induced testicular impairment in rats.

Impact of Adipose Tissue Depot Harvesting Site on the Multilineage Induction Capacity of Male Rat Adipose-Derived Mesenchymal Stem Cells: An In Vitro Study.

Recently, substantial attention has been paid toward adipose-derived mesenchymal stem cells (AdMSCs) as a potential therapy in tissue engineering and regenerative medicine applications. Rat AdMSCs (r-AdMSCs) are frequently utilized. However, the influence of the adipose depot site on the multilineage differentiation potential of the r-AdMSCs is still ambiguous. Hence, the main objective of this study was to explore the influence of the adipose tissue harvesting location on the ability of r-AdMSCs to express the stem-cell-related markers and pluripotency genes, as well as their differentiation capacity, for the first time. Herein, we have isolated r-AdMSCs from the inguinal, epididymal, peri-renal, and back subcutaneous fats. Cells were compared in terms of their phenotype, immunophenotype, and expression of pluripotency genes using RT-PCR. Additionally, we investigated their potential for multilineage (adipogenic, osteogenic, and chondrogenic) induction using special stains confirmed by the expression of the related genes using RT-qPCR. All cells could positively express stem cell marker CD 90 and CD 105 with no significant in-between differences. However, they did not express the hematopoietic markers as CD 34 and CD 45. All cells could be induced successfully. However, epididymal and inguinal cells presented the highest capacity for adipogenic and osteogenic differentiation (21.36-fold and 11.63-fold for OPN, 29.69-fold and 26.68-fold for BMP2, and 37.67-fold and 22.35-fold for BSP, respectively, in epididymal and inguinal cells (p < 0.0001)). On the contrary, the subcutaneous cells exhibited a superior potential for chondrogenesis over the other sites (8.9-fold for CHM1 and 5.93-fold for ACAN, (p < 0.0001)). In conclusion, the adipose tissue harvesting site could influence the differentiation capacity of the isolated AdMSCs. To enhance the results of their employment in various regenerative cell-based therapies, it is thus vital to take the collection site selection into consideration.

Adverse effects of methamphetamine on vital organs of male rats: Histopathological and immunohistochemical investigations.

Objectives: Methamphetamine (named crystal, ice, and crank), is a strong psychostimulant drug with addictive and neurotoxic properties. It is absorbed by various organs and induces tissue damage in abusers. Most METH studies have focused on the central nervous system and its effects on other organs have been neglected. Experimental investigations of animal models are used to provide significant additional information. We have studied the histopathological effects of methamphetamine in the brains, hearts, livers, testes, and kidneys of rats. Materials and Methods: Methamphetamine (0.5 mg/kg) was administered subcutaneously for 21 days. Immunohistochemistry was carried out with markers including glial fibrillary acidic protein (GFAP) for reactive astrocytes, vimentin as an intermediate filament in different cells, and CD45 marker for the detection of reactive microglia in the brain. Also, some samples were taken from livers, kidneys, hearts, and testes. Results: Degenerative changes and necrosis were the most common histopathological effects in the liver, kidneys, heart, testes, and brains of rats treated with methamphetamine. Immunohistochemical analyses by vimentin and GFAP markers revealed reactive microglia and astrocytes with the appearance of swollen cell bodies and also short, thickened, and irregular processes. Moreover, the number of CD45-positive cells was higher in this group. Reactive cells were more noticeable in the peduncles and subcortical white matter of the cerebellum. Conclusion: Our results showed the toxic effects of methamphetamine on the vital organs and induction of neurotoxicity, cardiomyopathy, renal damage, and infertility in male rats. We could not attribute observed hepatic changes to METH and further evaluation is needed.

Anti-aging effects of the pistachio extract on mesenchymal stem cells proliferation and telomerase activity.

PURPOSE: Using mesenchymal stem cells (MSCs) is a promising method in regenerative medicine. Limited proliferation and aging process of MSC are the most common problems in MSCs application. In the present study, we intend to investigate the anti-aging properties of pistachio pericarp in bone marrow-derived MSCs of old male rats. MATERIALS AND METHODS: First, 1000, 2000, and 3000 µg/mL AEPP were used to treat MSCs derived from bone marrow for 24 h at 37 °C. Then, cell viability, population doubling time, the percentage of senescent cells, telomere length, telomerase activity, and the expression of TRF1 and RAP1 when bone marrow-derived MSCs treated with AEPP were investigated. RESULTS: The results showed that cell viability increased when MSCs derived from bone marrow were treated with 2000 and 3000 µg/mL AEPP, indicating this extract may stimulate proliferation. The population doubling time was also enhanced with an increase in AEPP concentration. Importantly, an increase in AEPP concentration significantly reduced senescent cell percentage. Telomere length, telomerase activity, and the expression of anti-aging genes were significantly increased with the increase of AEPP dose. CONCLUSION: Taken together, AEPP has been used as a natural compound with excellent proliferation and anti-aging ability in MSCs. As new therapeutic candidates with promising effects, it can be used with high safety by multiplying cells and delaying the aging process. However, more studies are needed and the anti-aging effects of this extract should be well confirmed in animal models and clinical trials.

THE PECULIARITIES OF BIOCHEMICAL AND MORPHOLOGICAL CHANGES IN THE HEART OF THE CASTRATED RATS IN THE DEVELOPMENT OF ADRENALIN DAMAGE OF HEART.

OBJECTIVE: The aim of the study was to evaluate the state of oxidation processes and morphological changes in the heart of castrated rats during the development of epinephrine heart damage (EHD). PATIENTS AND METHODS: Materials and methods. The study was performed on 120 white male Wistar rats. The animals were divided into four series: 1 - control, 2 - castration. For EHD, rats were injected once intraperitoneally with a 0.18% solution of adrenaline hydrotartrate at the rate of 0.5 mg/kg of weight. Castration was performed under anesthesia. The concentration of diene and triene conjugates (DC, TC), Schiff's bases (SB), TBA-active products (TBA-ap), oxidatively modi"ed proteins (OMP), activity of superoxide dismutase (SOD) and catalase (CAT) were determined in the heart. A morphological study of preparations stained with Azantrichrome was carried out. All studies were performed in control, 1, 3, 7, 14 and 28 days after adrenaline injection. RESULTS: Results: In the I series DC and TC increased after 1 day of EHD, fell to control values after 3 days, and then had wave-like character (highest - after 14 days). SB decreased (minimal after 7 days), TBA-ap increase (maximal after 14 days). OMP370 increased after 1 and 3 days, after 7 days they did not differ from the control, after 14 days they were higher than in control, and after 28 days they decreased to the control values. OMP430 and OMP530were greater than the control indicators in all terms, except the last; the maximum was noted after 14 days. The activity of antioxidant enzymes was lower than the control indicators at all times of the study. Castration caused an increase of lipid peroxidation. After 7 days, DC and TC, were lower and SB - higher, than in the I series. Castration caused a decrease in OMP. In EHD all values of OMP, compared to the castrated control rats, were higher at all studed times Castration leads to increase of SOD, and decrase of CAT. All indicators of SOD and CAT exceeded the indicators of animals of the I series at all times of the study. Biochemical changes are consistent with morphological changes. After injection of epinephrine, severe vascular disorders, adventitia edema, perivasal edema, endothelial cell damage, dilatation of hemicapillaries, full blood vessels, stasis, hemorrhages in the surrounding tissues, and sclerosing of the walls of arteries and venules were observed. Cardiomyocytes were swollen, shortening, necrosis was observed, myocytolysis was noted. Edema of the stroma was noted. In the stroma, around the vessels, located cells of connective tissue elements were observed. Indicate more damage to the myocardium in the process of development of EHD in animals of the I series. CONCLUSION: Conclusions: Castration of rats causes an increase of lipid peroxidation products and CAT activity in the heart, but a decrease in the content of OMP. Adrenaline injection causes activation of lipid peroxidation and an increase in the content of OMP. During the development of EHD, the activity of antioxidants is significantly higher in II group. Biochemical changes are consistent with morphological, and indicate more damage to the myocardium in the development of EHD in animals of the I series.

The protective effect of red cabbage on water-soluble fractions of spent crankcase oil-induced alterations in lipid function biomarkers and atherogenic indices in male Albino rats.

Spent crankcase oil (SCO) contains a cocktail of metals and polycyclic aromatic hydrocarbons (PAHs), transferred to the associated water-soluble fractions (WSF); and low-dose heavy metals exposures could increase the triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) concentrations. Hence, this study estimated the changes in the lipid profile and atherogenic indices (AI) of male Wistar albino rats exposed to the WSF of SCO and treated with aqueous extracts (AE) of red cabbage (RC) for 60 and 90 days. Sixty-four male Wistar rats divided into 8 groups (8 animals each) were orally administered 1 mL of deionized water, 500 mg/kg AE of RC, 1 mL of 25%, 50%, and 100% WSF of SCO daily for 60 and 90 days, whereas alternate groups were given the stated percentages of the WSF and the AE. Serum TG, TC, LDL, and VLDL concentrations were then analyzed using appropriate kits and the AI estimated thereafter. Although the 60 days study presented a nonsignificant (P < 0.05) difference in the TG, VLDL, and high density lipoprotein (HDL)-C levels in all the exposed and treated groups, a significantly (P < 0.05) elevated TC and non-HDL was recorded for the 100% exposed group alone. Also, the LDL concentration of all exposed groups was higher than all treated groups. The findings at the 90th day was different, such that the 100% and 25% exposed only groups had elevated lipid profile (except HDL-C) concentrations and AI compared with other groups. RC extracts can act as good hypolipidemic agents in WSF of SCO hyperlipidemia potentiating events.

Duration of the diabetic state altered platelet indices from baseline values in a streptozotocin-induced rat model for type 1 diabetes mellitus.

BACKGROUND: Changes in platelet indices in naturally occurring type I diabetes mellitus (T1DM) have been described in several studies. In this study, platelet indices such as platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and MPV to PLT ratio were investigated according to diabetic duration after streptozotocin (STZ)-induced T1DM, as well as for their correlation with glucose. METHODS: Forty healthy adult Wistar rats were randomly assigned to four experimental groups of ten (5 rats of each sex), including the control group, the 7, 14, and 28 days diabetic groups (D7, D14, and D28, respectively). RESULTS: In diabetic groups, plasma glucose was significantly higher than in control (P < 0.01). D7, D14, and D28 groups presented significantly lower PLT than the control (P < 0. 01). A significant decrease in PCT was observed in D14 and D28 females (P < 0.05). Mean platelet volume was significantly higher in the D28 group than in to control. D28 females also showed a significant difference in PLT, MPV, and the MPV-to-PLT ratio compared with D7 females (P < 0.05). A comparison between D28 females and males showed a significant difference in PDW (P < 0.05). Both females and males showed a significant correlation between glucose and PLT, PCT, MPV, and the MPV-to-PLT ratio. CONCLUSIONS: Platelet indices change significantly with the duration of diabetes compared with the baseline values, and female and male rats did not have significant differences in platelet indices in any period except the 28 days.

In Vitro Evaluation of the Cytotoxic Potential of Thiosemicarbazide Coordinating Compounds in Hepatocyte Cell Culture.

Cancer is a global medical problem and, despite research efforts in the field of tumor treatment, there is currently a shortage of specific anticancer drugs. Most anticancer drugs show significant side effects. The liver is the organ that has central functions in drug metabolism, being a major target of the harmful action of anticancer compounds. In this context, it is essential to evaluate the cytotoxic effects of potential anticancer substances. Therefore, hepatotoxicity and hepatocyte viability were determined in vitro to evaluate the action of seven new local thiosemicarbazide coordination compounds (CCT) on normal liver cells. Doxorubicin was used as a reference substance. The control group consisted of hepatocytes not exposed to CCT action. The cell viability of hepatocytes treated with CCT decreased significantly by 5-12% compared to the control, but was statistically significantly higher by 5-14% compared to doxorubicin, except after CMD-8 and CMT-67 influence, when it does not change. Thus, new local CCT had a selective effect on hepatocytes in vitro and were less hepatotoxic compared to doxorubicin, which may be the basis for further study of its potential in anticancer drugs.

Impact of Mephedrone on Fear Memory in Adolescent Rats: Involvement of Matrix Metalloproteinase-9 (MMP-9) and N-Methyl-D-aspartate (NMDA) Receptor.

Treatment of Post-Traumatic Stress Disorder (PTSD) is complicated by the presence of drug use disorder comorbidity. Here, we examine whether conditioned fear (PTSD model) modifies the rewarding effect of mephedrone and if repeated mephedrone injections have impact on trauma-related behaviors (fear sensitization, extinction, and recall of the fear reaction). We also analyzed whether these trauma-induced changes were associated with exacerbation in metalloproteinase-9 (MMP-9) and the GluN2A and GluN2B subunits of N-methyl-D-aspartate (NMDA) glutamate receptor expression in such brain structures as the hippocampus and basolateral amygdala. Male adolescent rats underwent trauma exposure (1.5 mA footshock), followed 7 days later by a conditioned place preference training with mephedrone. Next, the post-conditioning test was performed. Fear sensitization, conditioned fear, anxiety-like behavior, extinction acquisition and relapse were then assessed to evaluate behavioral changes. MMP-9, GluN2A and GluN2B were subsequently measured. Trauma-exposed rats subjected to mephedrone treatment acquired a strong place preference and exhibited impairment in fear extinction and reinstatement. Mephedrone had no effect on trauma-induced MMP-9 level in the basolateral amygdala, but decreased it in the hippocampus. GluN2B expression was decreased in the hippocampus, but increased in the basolateral amygdala of mephedrone-treated stressed rats. These data suggest that the modification of the hippocampus and basolateral amygdala due to mephedrone use can induce fear memory impairment and drug seeking behavior in adolescent male rats.

Male reproductive system and simulated high-altitude environment: preliminary results in rats.

This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.