Assessment of serum calprotectin as a marker of inflammation in cattle with traumatic reticuloperitonitis.

Calprotectin (CP) is an inflammatory marker. The aim of the current study was to investigate oxidative stress and changes in CP in cattle with traumatic reticuloperitonitis (TRP). The study was divided into two groups, experimental (TRP) and healthy control group, with 10 animals in each group. Total leucocyte count, neutrophil and lymphocyte counts were higher in the TRP group compared to the control group and this increase was statistically significant (P < 0.001). The level of malondialdehyde (MDA) in TRP group was statistically significantly higher than the control group (P < 0.001). The level of glutathione (GSH) in the TRP group was statistically significantly lower than in the control group (P < 0.001). Serum Amyloid A (SAA) and CP values were higher in the TRP group and this difference was statistically significant (P < 0.001). It was concluded as a result of ROC analysis that CP, which has similar values with SAA, can be used diagnostically to confirm the inflammatory status in cattle with TRP.

Assessment of toxicological effects of favipiravir (T-705) on the lung tissue of rats: An experimental study.

This study aimed to present new data on the side effects of favipiravir on healthy lung tissue and the respiratory system. In the study, two different durations (5 and 10 days) were preferred to determine the effect of favipiravir treatment due to clinical improvement rates of approximately 5 and 10 days during the use of favipiravir in COVID-19 patients. In addition, after 10 days of favipiravir treatment, animals were kept for 5 days without any treatment to determine the regeneration of lung tissues. Favipiravir was administered to rats by oral gavage at a daily dose of 200 mg/kg for 5 and 10 days, as in previous studies. At the end of the experiment, the histopathological and biochemical effects of favipiravir in the lung tissue were investigated. The data obtained from the study showed that favipiravir increased oxidative stress parameters, expression of apoptotic markers, and pro-inflammatory markers in lung tissue. Since malondialdehydes is an oxidant parameter, it increased in favipiravir-administered groups; It was determined that the antioxidant parameters glutathione, superoxide dismutase, glutathione peroxidase, and catalase decreased. Other markers used in the analysis are Bcl-2, Bax, NF-κB, interleukin (IL)-6, Muc1, iNOS, P2X7R, IL-6 and caspase-3. The levels of Bax, caspase-3, NF-κB, IL-6, Muc1, and P2X7R were increased in the Fav-treated groups compared with the control. However, the levels of Bcl-2 decreased in the Fav-treated groups. The present study proves that favipiravir, widely used today, causes side effects in lung tissue.

Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress.

Paclitaxel (PTX) is widely used to treat a number of malignancies, although it has toxic side effects. Hesperidin (HES) has a wide range of biological and pharmacological properties, including anti-inflammatory and antioxidant abilities. This research aims to investigate the role of HES in PTX-induced testicular toxicity. For 5 days, 2 mg/kg/bw i.p. of PTX was administered to induce testicular toxicity. Rats were administered oral dosages of 100 and 200 mg/kg/bw HES for 10 days after PTX injection. The mechanisms of inflammation, apoptosis, endoplasmic reticulum (ER) stress, and oxidants were investigated using biochemical, genetic, and histological techniques. As a result of PTX administration, decreased antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities and increased malondialdehyde level were regulated, and the severity of oxidative stress was reduced. NF-κB, IL-1ß and TNF-α levels, which are among the increased inflammation parameters caused by PTX, decreased with HES administration. Although AKT2 gene expression decreased in PTX administered rats, it was determined that HES administration up-regulated AKT2 mRNA expression. Anti-apoptotic Bcl-2 decreased with PTX administration, and apoptotic Bax and Caspase-3 increased while HES administration reverted these effects towards control level. As a result of toxicity, the increase in ATF6, PERK, IRE1α, GRP78 levels caused prolonged ER stress, and this activity was diminished with HES and tended to regress. While all data were evaluated, Paclitaxel caused damage by increasing inflammation, apoptosis, ER stress and oxidant levels in testicular tissue, and Hesperidin showed a protective effect by correcting the deterioration in these levels.

Chrysin mitigates diclofenac-induced hepatotoxicity by modulating oxidative stress, apoptosis, autophagy and endoplasmic reticulum stress in rats.

BACKGROUND: Diclofenac (DF) is a non-steroidal anti-inflammatory drug (NSAID) generally prescribed for the treatment of pain. In spite of the widespread use of DF, hepatotoxicity has been reported after its administration. The current study discloses new evidence as regards of the curative effects of chrysin (CHR) on DF-induced hepatotoxicity by regulating oxidative stress, apoptosis, autophagy, and endoplasmic reticulum (ER) stress. METHODS: The animals were separated into five different groups. Group-I was in control. Group-II received CHR-only (50 mg/kg bw, p.o.) on all 5 days. Group-III received DF-only (50 mg/kg bw, i.p.) on 4th and 5th day. Group-IV received DF (50 mg/kg bw) + CHR (25 mg/kg, bw) and group-V received DF (50 mg/kg, bw) + CHR (50 mg/kg, bw) for 5 days. RESULTS: DF injection was associated with increased MDA while reduced GSH level, activities of superoxide dismutase, glutathione peroxidase, and catalase and mRNA levels of HO-1 and Nrf2 in the liver. DF injection caused apoptosis and autophagy in the liver by up-regulating caspase-3, Bax, LC3A, and LC3B levels and down-regulating Bcl-2. DF also caused ER stress by increasing mRNA transcript levels of ATF-6, IRE1, PERK, and GRP78. Additionally, it was observed that DF administration up-regulated MMP2 and MMP9. However, treatment with CHR at a dose of 25 and 50 mg/kg considerably ameliorated oxidative stress, apoptosis, autophagy, and ER stress in liver tissue. CONCLUSION: Overall, the data of this study indicate that liver damage associated with DF toxicity could be ameliorated by CHR administration.

Investigation of hemogram, oxidative stress, and some inflammatory marker levels in neonatal calves with escherichia coli and coronavirus diarrhea.

Calf diarrhea is the most common disease affecting calves in the neonatal period resulting in economic losses. Although predisposing factors play a role in the etiology of the disease, in most cases, different pathogens are involved in the development of the infection. In this study, hemogram data, glutathione and malondialdehyde levels were examined to determine lipid peroxidation and glutathione levels in E. coli- and coronavirus-infected calves. Serum amyloid A and calprotectin levels were also analyzed to determine inflammatory status. The study included a total of 45 female Montofon calves aged 0-1 week, including the E. coli group (15 calves), the coronavirus group (15 calves), and the control group (15 calves). Analysis revealed that total leukocyte, neutrophil, lymphocyte, malondialdehyde, serum amyloid A, and calprotectin levels increased in the coronavirus-infected calves compared with the E. coli group and the control group. In contrast, the levels of glutathione, one of the antioxidant markers, decreased. In conclusion, the main findings related to the determination of inflammation and oxidative status were characterized by the presence of E. coli and coronavirus diarrhea, and it is suggested that future studies may be guided by the fact that inflammatory conditions are higher in viral disease than in bacterial infection.

The impact of Nrf2/HO-1, caspase-3/Bax/Bcl2 and ATF6/IRE1/PERK/GRP78 signaling pathways in the ameliorative effects of morin against methotrexate-induced testicular toxicity in rats.

BACKGROUND: Methotrexate (MT) is a broadly used chemotherapeutic drug however its clinical use is confronted with several forms of toxicities containing testicular damage. The current study assessed the ameliorative effects of morin on MT-induced testicular damage with the investigation of its mechanism and the potential involvement of oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in such protection. METHODS: The animals were divided into 5 distinct groups (7 rats in each group). Group 1 was control group, group 2 received MT-only (20 mg/kg bw), group 3 received orally morin-only (100 mg/kg bw), group 4 received MT (20 mg/kg bw) + morin (50 mg/kg bw) and group 5 received MT (20 mg/kg bw) + morin (100 mg/kg). In this study, morin was administered orally for 10 days, while MT was administered intraperitoneally on the 5th day. RESULTS: MT intoxication was linked with augmented MDA while decreased GSH levels, the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase and mRNA levels of HO-1 and Nrf2 in the testis tissues. MT injection caused inflammation in the testicular tissue via up-regulation of MAPK14, NFκB, TNF-α and IL-1ß. MT application also caused apoptosis and endoplasmic reticulum stress in the testis tissue via increasing mRNA transcript levels of Bax, caspase-3, PERK, IRE1, ATF-6, GRP78 and down-regulation of Bcl-2. CONCLUSION: Treatment with morin at a dose of 50 and 100 mg/kg considerably mitigated oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in the testicular tissue indicating that testicular damage related to MT toxicity could be modulated by morin administration.

Protective effect of naringin against oxaliplatin-induced peripheral neuropathy in rats: A behavioral and molecular study.

Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1ß, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase (nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.

Hesperidin Attenuates Oxidative Stress, Inflammation, Apoptosis, and Cardiac Dysfunction in Sodium Fluoride-Induced Cardiotoxicity in Rats.

Excessive fluoride intake has been reported to cause toxicities to brain, thyroid, kidney, liver and testis tissues. Hesperidin (HSP) is an antioxidant that possesses anti-allergenic, anti-carcinogenic, anti-oxidant and anti-inflammatory activities. Presently, the studies focusing on the toxic effects of sodium fluoride (NaF) on heart tissue at biochemical and molecular level are limited. This study was designed to evaluate the ameliorative effects of HSP on toxicity of NaF on the heart of rats in vivo by observing the alterations in oxidative injury markers (MDA, SOD, CAT, GPX and GSH), pro-inflammatory markers (NF-κB, IL-1ß, TNF-α), expressions of apoptotic genes (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic markers (Beclin 1, LC3A, LC3B), expression levels of PI3K/Akt/mTOR and cardiac markers. HSP treatment attenuated the NaF-induced heart tissue injury by increasing activities of SOD, CAT and GPx and levels of GSH, and suppressing lipid peroxidation. In addition, HSP reversed the changes in expression of apoptotic (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic and inflammatory parameters (Beclin 1, LC3A, LC3B, NF-κB, IL-1ß, TNF-α), in the NaF-induced cardiotoxicity. HSP also modulated the gene expression levels of PI3K/Akt/mTOR signaling pathway and levels of cardiac markers (LDH, CK-MB). Overall, these findings reveal that HSP treatment can be used for the treatment of NaF-induced cardiotoxicity.

Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy.

Fluoride is an element with toxic properties and has been proven to have some adverse effects on many soft tissues, including brain tissue. This study aims to evaluate the protective effects of hesperidin on sodium fluoride (NaF)-induced neurotoxicity in rats by biochemical and molecular methods. The animals were randomly divided into five groups of seven rats each as Control, hesperidin, NaF (600 ppm), NaF + hesperidin (100 mg/kg, b.w.), and NaF + hesperidin (200 mg/kg, b.w.), respectively; orally for two weeks. Hesperidin reduced lipid peroxidation and increased activities of SOD, CAT and GPx and levels of GSH in NaF-induced brain tissue. Hesperidin also showed anti-inflammatory and anti-autophagic effects by decreasing levels of NF-κB, IL-1B, TNF-α, Beclin-1, LC3A, and LC3B in NaF-induced brain tissue. Moreover, hesperidin was able to down-regulate the mRNA transcript levels of apoptosis and endoplasmic reticulum stress markers such as caspase-3, Bax, Bcl-2, PERK, IRE1, ATF6, and GRP78 in NaF-induced neurotoxicity. Hesperidin also reduced the adverse effects caused by NaF by modulating the PI3K/Akt/mTOR signaling pathway. These results demonstrate that hesperidin exhibits neuroprotective effects against NaF-induced neurotoxicity in rats by ameliorating inflammation, apoptosis, autophagy, and endoplasmic reticulum stress.

Neuroprotective effects of carvacrol against cadmium-induced neurotoxicity in rats: role of oxidative stress, inflammation and apoptosis.

Cadmium (Cd), is a heavy metal reported to be associated with oxidative stress and inflammation. In this paper, we investigated the possible protective effects of carvacrol against Cd-induced neurotoxicity in rats. Adult male Sprague Dawley rats were treated orally with Cd (25 mg/kg body weight) and with carvacrol (25 and 50 mg/kg body weight) for 7 days. Carvacrol decreased the levels of malondialdehyde (MDA), glial fibrillary acidic protein (GFAP) and monoamine oxidase (MAO), and significantly increased the levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in brain tissue. Additionally, carvacrol alleviated the in levels of inflammation and apoptosis related proteins involving p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), B-cell lymphoma-3 (Bcl-3), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), myeloperoxidase (MPO), prostaglandin E2 (PGE2), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), cysteine aspartate specific protease-3 (caspase-3) and Bcl-2 associated X protein (Bax) in the Cd-induced neurotoxicity. Carvacrol also decreased the mRNA expression of matrix metalloproteinases (MMP9 and MMP13), as well as 8-hydroxy-2'-deoxyguanosine (8 - OHdG) level, a marker of oxidative DNA damage. Collectively, our findings indicated that carvacrol has a beneficial effect in ameliorating the Cd-induced neurotoxicity in the brain of rats.

Evaluation of the protective effects of morin against acrylamide-induced lung toxicity by biomarkers of oxidative stress, inflammation, apoptosis, and autophagy.

Acrylamide (ACR) has genotoxic, neurotoxic, and carcinogenic effects. From past to present, various plants or their products have been used for therapeutic purposes such as morin. It was aimed to detect possible protective effects of morin vs ACR-induced lung toxicity. The rats, treated with ACR alone or with morin for 10 consecutive days, were included in the study. A broad variety of biomarkers related to oxidative stress, apoptosis, autophagy, and inflammatory responses were evaluated. ACR increased malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB), Beclin-1, IL-1ß, bcl-2 associated X protein (Bax), caspase-3, light chain 3-A (LC3-A), and light chain 3-B (LC3-B) levels but reduced mammalian target of rapamycin (mTOR), b-cell lymphoma-2 (Bcl-2), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH) in lung tissues. The morin had effects on the level of these molecules in a way that is opposite to ACR. While ACR-induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, the morin reduced ACR-induced lung damage. PRACTICAL APPLICATIONS: ACR is a toxic chemical produced by frying, baking, roasting, or grilling foods with high starch content and has genotoxic, neurotoxic, and carcinogenic effects. As an antioxidant compound, the morin is obtained from plants or their products. It was aimed to detect possible protective effects of morin against ACR-induced lung toxicity. It was detected that ACR-induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, but the morin reduced ACR-induced lung damage.

Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti-inflammatory, and antiapoptotic properties.

In the present study, the protective effects of chrysin (CHR) against testicular damage caused by lead acetate (PbAc) were examined. In this way, 30 min after rats were given 25 and 50 mg/kg/b.w CHR orally for seven consecutive days, 30 mg/kg/b.w PbAc was administered orally. In biochemical analysis of testicular tissue, it was found that PbAc-reduced antioxidant parameters [glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)], while it increased lipid peroxidation, inflammatory markers [nuclear factor kappa-B (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), and inducible nitric oxide synthase (iNOS)], and 8-hydroxy-2'-deoxyguanosine (8-OHdG). In the immunohistochemical examination, it was determined that PbAc increased the expression of tumor necrosis factor-α (TNF-α) and caspase-3. Accordingly, PbAc was found to cause a decrease in sperm motility and an increase in the percentage of dead sperm. However, it has been observed that CHR relieves oxidative stress due to its antioxidant properties, thus protecting against inflammation and apoptosis. It also allowed the CHR sperm parameters to return to control group levels. The results revealed that CHR could be a natural substance to be used in Pb-induced testicular toxicity. PRACTICAL APPLICATIONS: Lead (Pb) is an important environmental contaminant heavy metal. Pb is believed to reduce fertility in men. Oxidative stress plays a significant role in the damage caused by Pb to testicular tissue. CHR is an antioxidant substance that occurs naturally in various plants and has various pharmacological properties. In the present study, it was investigated whether CHR has a protective effect against testicular toxicity induced by PbAc. The results revealed that in rats, CHR protects the testicular tissue from PbAc toxicity by showing antioxidant, anti-inflammatory and anti-apoptotic effects, thus bringing sperm parameters closer to normal.