Promising the potential of ß-caryophyllene on mercury chloride-induced alteration in cerebellum and spinal cord of young Wistar albino rats.

Mercury chloride (ME) is a chemical pollutant commonly found in the environment, which can contribute to undesirable health consequence worldwide. The current study investigated the detrimental impact of ME on the cerebellum and spinal cord tissues in 6-8-week-old female rats. We also evaluated the neuroprotective efficacy of ß-caryophyllene (BC) against spinal and cerebellar changes caused by ME. Thirty-five young Wistar albino rats were randomly chosen and assigned into five groups: control (CO), olive oil (OI), ME, BC, ME + BC. All samples were analysed by means of unbiased stereological, biochemical, immunohistochemical, and histopathological methods. Our biochemical findings showed that SOD level was significantly increased in the ME group compared to the CO group (p < 0.05). We additionally detected a statistically significant decrease in the number of cerebellar Purkinje cells and granular cells, as well as spinal motor neuron in the ME group compared to the CO group (p < 0.05). In the ME + BC group, the number of Purkinje cells, granular cells, and spinal motor neurons was significantly higher compared to the ME group (p < 0.05). Decreased SOD activity in the ME + BC group was also detected than the ME group (p < 0.05). Immunohistochemical (the tumour necrosis factor-alpha (TNF-α)) and histopathological examinations also exhibited crucial information in each of the group. Taken together, ME exposure was associated with neurotoxicity in the cerebellum and spinal cord tissues. BC treatment also mitigated ME-induced neurological alteration, which may imply its potential therapeutic benefits.

Protective effect of misoprostol against paclitaxel-induced cardiac damage in rats.

OBJECTIVE: One of the most critical reasons for limiting cancer treatment is the toxic effects of anti-cancer drugs on healthy tissues and organs. This study aims to investigate the possible protective effects of misoprostol (MS) against the damage that arises from paclitaxel (PT), an anti-cancer pharmacological agent, in the rat heart using histopathological and biochemical analyses. METHODS: In this study, four groups, each containing seven animals, were formed by random selection from 28 Sprague Dawley female rats. Control group rats were administered 1 ml of normal saline orally and intraperitoneally (i.p.) for six days. While the PT group rats were administered PT at a dose of 2 mg/kg intraperitoneally (i.p.) on days 0, 2, 4, and 6, the MS group was administered MS at a dose of 0.2 mg/kg in 1 ml normal saline by oral gavage for six days. PT and MS were administered to the PT + MS group rats in the same dose and route as the previous groups. RESULTS: Administration of PT increased serum lactate dehydrogenase (LDH), cardiac troponin I (cTn-I), creatine kinase isoenzyme MB (CK-MB), and brain natriuretic peptide (BNP) levels. PT administration also decreased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the heart tissue while increasing the level of malondialdehyde (MDA) (p < 0.05). In histopathological examinations, pathological changes, such as edema, congestion, hemorrhage, apoptosis, and degeneration, occurred in the heart tissue of PT-treated rats. The negative changes in histopathological and biochemical parameters that occurred in the PT group were almost not observed in the PT + MS group (p < 0.005). CONCLUSION: When the findings were evaluated, it was concluded that MS protects the heart tissue from the harmful effects of PT, probably due to its antioxidant, anti-apoptotic and TNF-alpha suppressive effects.

Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel.

One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-α), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group. The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNF-α suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively.

Effect of different pasture species on welfare and behavior of slow-growing broiler chickens in free-range production system.

This study investigated the effect of various pasture species on the welfare and behavior of slow-growing broiler chickens in the free-range production system. After 21 days completely indoors, the birds were permitted access to outdoor pens cultivated with one of the following pasture treatments: Medicago sativa (A), Trifolium repens (WC), Lolium perenne (PR), and a mixture (Mix, A + WC + PR). The range availability was restricted between 08:30 and 16:30 daily. It was found that pasture type had a significant effect on the fluctuating asymmetry of the face and radius length (P < 0.01). Duration of tonic immobility and blood parameters did not differ among the pasture species and between sexes at 11 weeks of broiler age (P > 0.05). Pasture treatment had no significant effect on broiler behaviors (P > 0.05). However, the age of broilers had a significant effect on pecking, dustbathing, and scratching (P < 0.01). Pecking behavior was affected by the time of the day; morning and afternoon (P < 0.01). Location had a significant effect on pecking and stretching behaviors (P < 0.01). In the study, dustbathing behavior was significantly affected by the interaction between location and age (P < 0.01), age and time of the day (P < 0.01), and location, age, and time of the day (P < 0.05). Scratching behavior was significantly affected by the interaction between location and time of the day (P < 0.05) and location, age and time of the day (P < 0.01). Stretching behavior was significantly affected by the interaction between location and age (P < 0.05) and location, age and time of the day (P < 0.05). It was concluded that access to the studied pasture species does not affect the evaluated welfare traits and observed behaviors. Therefore, it is suggested that other pasture species should be investigated to identify their effect on slow-growing strains in the free-range production system.

A synthetic prostaglandin E1 analogue, misoprostol, ameliorates paclitaxel-induced oxidative damage in rat brain.

The main objective of our study was to examine the protection of misoprostol (MP) on paclitaxel (PAX) side effects in rat brains. Twenty-eight female Sprague-Dawley rats were provided to form 4 groups, each containing seven rats: the control group was given 1 mL of 0.9% NaCl intraperitoneally (i.p.) and 1 mL of 0.9% NaCl orally for six days. In treatment groups, each rat was injected with 2 mg/kg PAX i.p. on days 0, 2, 4, and 6 of the study, and 0.2 mg/kg/day MP was given by oral gavage for six days. Levels of malondialdehyde (MDA) and glutathione (GSH), activities of superoxide dismutase (SOD), and catalase (CAT) of tissue samples were measured. In immunohistochemical analyzes, it was observed that tumor necrosis factor-alpha (TNF-α) and cleaved caspase-3 expression in the cerebellum hippocampus and cerebral cortex were increased in the PAX group compared to the other groups. The increase in TNF-α and cleaved caspase-3 expression detected in PAX group rats were significantly decreased in the PAX + MP group. The results obtained in this study confirm the hypotheses that PAX can increase apoptosis in brain tissue both directly and through cytokines such as TNF-α. It also shows that MP can be used as a protective and therapeutic pharmacological agent against the harmful effects of PAX on brain tissue. In addition, it seems that the use of MP can improve PAX-induced brain damage by preventing oxidative damage.

The ameliorative effects of thymoquinone and beta-aminoisobutyric acid on streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiac dysfunction observed in a patient with diabetes that may lead to heart failure. No specific treatment has yet been tested in DCM. Therefore, in this study, it was investigated that the potential of thymoquinone (TYM) and beta-aminoisobutyric acid (BAIBA) to treat DCM. Five groups (n = 7) were formed, namely control, diabetes, TYM, BAIBA and TYM + BAIBA, with a random selection from 35 adult male rats. Diabetes mellitus was induced by intraperitoneal administration of 50 mg/kg streptozotocin to all groups except the control. After establishing experimental diabetes, TYM (20 mg/kg/day) and BAIBA (100 mg/kg/day) were administered alone or in combination with other groups other than the control and diabetes groups for five weeks by gavage. Serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, and tissue malondialdehyde levels increased significantly, and tissue glutathione levels decreased in the diabetes group compared to the control group. An increase in the expression of tumor necrosis factor-α in the myocardium and the rate of fibrosis and apoptosis were found in the histopathological analysis. In the TYM and BAIBA groups, all pathological changes observed in the diabetes group improved significantly. The therapeutic effects of these agents on DCM are probably due to their antihyperglycemic, antidiabetic, antioxidant, and anti-inflammatory effects. The present results suggested that TYM and BAIBA have the potential therapeutic effects on DCM that were used alone or combined.

Thymoquinone improves testicular damage and sperm quality in experimentally varicocele-induced adolescent rats.

The aim of this study was to investigate the protective and therapeutic effects of thymoquinone against the negative effects of varicocele on testicular tissue and sperm morphology. Five groups were formed by random selection from a total of 40 adult male Wistar rats (n = 8). Thymoquinone (5 mg/kg/day) was administered intraperitoneally to the varicocele-dimethyl sulfoxide-olive oil-thymoquinone (VT) group and the sham-thymoquinone group. At the end of the 60th day, all groups were anaesthetised and the left testis was removed from the body quickly. One half of the testis tissue, which was divided into two, was separated for biochemical and Western blot analysis, while the other half were fixed in Bouin's fixative. As a result of biochemical, molecular and histopathological analyses, a statistically significant increase was found in the varicocele group testicular tissues in the malondialdehyde level, apoptotic index, Bax expression, cytochrome c expression and Bax/Bcl-2 ratio compared with the sham group. In addition, histopathological changes characterised by partial or complete degeneration of the germinal epithelium were observed in the seminiferous tubules in the same group. Total oxidant status level and sperm count with abnormal morphology increased in varicocele group, whereas total antioxidant status level decreased. In the VT group, all of the biochemical, molecular and histopathological changes detected in the varicocele group were statistically significantly reduced. When the findings obtained in this study are evaluated, it can be said that thymoquinone has the potential to be used as a preventive and therapeutic pharmacological agent in the medical treatment of varicocele. Although the exact mechanism of action of thymoquinone has not been fully elucidated, the findings obtained in this study support the view that thymoquinone showed a cytoprotective effect by reducing apoptosis, oxidative stress and lipid peroxidation.

The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity.

AIMS: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (ß) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-қB signaling pathway. MAIN METHODS: Human pancreatic ß cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 µM), doxorubicin (2 µM) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. KEY FINDINGS: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-кB pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-кB signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. SIGNIFICANCE: Melatonin could be a good candidate against pancreatic ß cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-кB pathways.

The effects of prepubertal epididymal ligation upon the rat testis.

BACKGROUND: Previous researches about the effects of epididymal obstruction on the testes are contradictory, and the mechanism harmful effect of male duct system obstruction on seminiferous tubules still remains unclear. OBJECTIVE: The aim of this study was to investigate the effects of epididymal obstruction in prepubertal rats on the testis. MATERIALS AND METHODS: 15 days of age, the young rats were divided at random in two groups for epididymal ligation (n=25) or sham operation (n=15). Both groups were sacrificed at 21, 35, 56, 90, 120 days. The testis were removed, fixed in Bouin's fixative and embedded in paraffin wax. The tissues were sectioned at 5 µm and stained with haematoxylin-eosin and triple stain. RESULTS: In ligated rats the first histological alterations were detected at 56 days. These degenerative changes included increase at the seminiferous tubule diameter and basal membrane thickness, decrease at the germinal epithelium thickness, depletion of spermatids and presence of multinucleated spermatids. In 90 and 120 days ligation groups; germ cells greatly reduced in number. CONCLUSION: progressive degenerative alterations occurred in the seminiferous tubules after prepubertal epididymal obstruction but these degenerative alterations are not observed until puberta and in the seminiferous tubules that showed extensive degeneration, seminiferous epithelium was composed mainly of Sertoli cells.

Effects of prepubertal epididymal ligation on the androgen receptor distribution of the rat testis.

OBJECTIVE: To investigate the effects of prepubertal epididymal obstruction on the androgen receptor (AR) distribution in the testis. STUDY DESIGN: Young rats were randomly divided into 2 groups for epididymal ligation and sham operation. In the ligation group the corpus epididymides were ligated bilaterally, while only laparatomy operation was performed in the sham group. Both groups were sacrificed at 21, 35, 56, 90 and 120 days. The testes were removed, fixed in Bouin's fixative and embedded in paraffin wax. The tissues were sectioned at 5 microm, stained with hematoxylin-eosin, and a microwave simulated antigen retrieval technique was used for immunohistochemistry. RESULTS: The first pathological alterations in the testes of ligated animals were observed at 56 days, and after that the alterations continued progressively. In 90 and 120 days of ligation the number of germ cells was reduced and seminiferous epithelium was mainly composed of Sertoli cells. AR immunostaining was detected in the nuclei of peritubular myoid cells, Sertoli cells, Leydig cells and pericytes but not in germ cells of the sham group rats. Except for the Sertoli cells, immunostaining properties of the ligation group rats were similar with those of the sham group. CONCLUSION: Progressive degenerative alterations occurred in the seminiferous tubules after prepubertal epididymal obstruction. The nuclei of Sertoli cells were not AR immunostaining in extensively degenerated seminiferous tubules.