Investigation of oxidative, inflammatory and apoptotic effects of favipiravir use alone and combined with vitamin C on brain tissue of elderly rats.

Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats' brain tissue and the possible mechanisms of these effects. A total of 30 rats used in the study were randomly divided into 5 equal groups and the first group was kept as the control group. High-dose (100 mg/kg) or low-dose (20 mg/kg) favipiravir was administered alone or in combination with vitamin C (150 mg/kg) to other groups. Administration of both high and low doses of favipiravir significantly increased TBARS levels in brain tissue of aged rats. Similarly, both high and low doses of favipiravir led to significant increases in Bcl-2 and caspase-3 relative mRNA expression. However, only low dose favipiravir caused a significant increase in iNOS and IL-1ß relative mRNA expression levels. Similar results were also observed in histopathological examinations. However, co-administration of vitamin C with favipiravir attenuated some of the adverse effects of favipiravir. In conclusion, in this study, it was shown that the use of favipiravir caused some adverse effects through oxidative, inflammatory and apoptotic processes in the brain tissue of aged rats, and the potential of vitamin C to alleviate these effects.

The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats.

Background: Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC).Methods: A total of 40 Sprague-Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes.Results: FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (p < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (p < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (p < .05).Conclusion: FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.

Nerolidol attenuates dehydroepiandrosterone-induced polycystic ovary syndrome in rats by regulating oxidative stress and decreasing apoptosis.

AIMS: Although nerolidol (NRL) is a naturally occurring sesquiterpene alcohol with many pharmacological activities, its role in dehydroepiandrosterone DHEA-induced polycystic ovary syndrome PCOS is unknown. This study aims to explore the potential beneficial effects and underlying molecular mechanisms of nerolidol treatment on polycystic ovary syndrome. MAIN METHODS: Pre-pubertal female Sprague-Dawley rats were randomly assigned into four groups (n = 8/group); group I: control; group II: PCOS; group III: P + NRL; group IV: NRL. Biochemical parameters related to oxidative stress, inflammation, apoptosis, and hormones were estimated in the blood and ovarian tissues. Histopathological, ultrastructural, and immunohistochemical analyses were performed. Bax, P53, Cas-3, and Bcl-2 gene expression levels were detected with RT-PCR. The membrane array analysis detected chemokine, cytokine, and growth factor protein profiles. KEY FINDINGS: In light of the available data, it can deduce that nerolidol has a significant ameliorating effect on lipid peroxidation, oxidative stress, inflammation, histopathological damage, and apoptosis accompanying PCOS in female rats. SIGNIFICANCE: PCOS is not only a reproductive pathology but also a systemic condition and its etiopathogenesis is still not fully understood. Since changes in PCOS have important long-term effects on health, this study evaluated the efficacy of nerolidol, a phytotherapeutic for the control of biochemical, apoptotic, histopathological, and metabolic changes.

The protective effects of capsaicin on oxidative damage-induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats.

The present study aimed to investigate the protective role of capsaicin in a rat model of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD)-induced toxicity. Exposure to TCDD which is an environmental toxicant causes severe toxic effects in the animal and human tissues. Therefore, the potential protective effect of capsaicin in TCDD-induced organ damage was investigated in rats by measuring thiobarbituric acid reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the heart, liver, and kidney tissues for oxidant/antioxidant balance. Thirty-two healthy adults (250-300 g weight and 3-4 months old) male Wistar albino rats were randomly distributed into four equal groups (n = 8): Control, CAP, TCDD, TCDD + CAP. A dose of 2 µg/kg TCDD or a dose of 25 mg/kg capsaicin were dissolved in corn oil and orally administered to the rats for 30 days. The results indicated that TCDD-induced oxidative stress by increasing the level of TBARS and by decreasing the levels of GSH, and SOD activity in the tissues of rats. However, capsaicin treatment was significantly decreased TBARS levels and was significantly increased GSH level and SOD activity (p < 0.05). In addition, capsaicin (25 mg/kg) significantly attenuated TCDD-induced histopathological alteration associated with oxidative stress in the heart, liver, and kidney tissues (p < 0.05). As capsaicin regulates oxidative imbalance and attenuates histopathological alterations in the rat tissues, it may be preventing agents in TCDD toxicity.

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats.

PURPOSE: To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyclophosphamide side effects. METHODS: A 40 healthy adult female Wistar albino rats were used in this study. Rats were randomly divided into four groups to determine the effects of curcumin and capsaicin against Cyclophosphamide side effects on the uterus (n=10 in each group); Group 1 was the control group (sham-operated), Group 2 was the cyclophosphamide group, Group 3 was the cyclophosphamide + curcumin (100mg/kg) group, and Group 4 was the cyclophosphamide + capsaicin (0.5 mg/kg) group. RESULTS: Increased tissue oxidative stress and histological damage in the rat uterus were demonstrated due to the treatment of systemic cyclophosphamide chemotherapy alone. The level of tissue oxidant and antioxidant markers and histopathological changes were improved by the treatment of curcumin and capsaicin. CONCLUSION: Cytotoxic effects of natural alkylating chemotherapeutic agents like cyclophosphamide on the uterus can be prevented by curcumin and capsaicin.

The beneficial effects of 18ß-glycyrrhetinic acid on the experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mouse model.

AIM: The aim of this study was to investigate the beneficial effects of 18ß-glycyrrhetinic acid (GA) on the experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. GA is a natural substance found in the root of licorice and is used in traditional Chinese medicine. It has many pharmacological activities such as antioxidant, anti-inflammatory, and anti-cancer effects. MATERIALS AND METHODS: A total of 40 C57BL/6 mice were divided equally into four groups: (1) Control, (2) EAE, (3) GA and (4) GA + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, mice were treated with GA at doses of 100 mg/kg/day for 7 days intraperitoneally. RESULTS: To our results, oxidative stress and lipid peroxidations (elevated TBARS levels, decreased GPx, SOD, CAT, and GSH levels) were significantly (p < .01) increased, causing EAE in brain tissue. Also, histopathological damage (Caspase-3 and IL-17 activity, p ≤ .01) and cytokine levels (TNF-α and IL-1ß, p < .01) were induced with EAE in mice brain tissue. On the other hand, GA treatment significantly (p < .01) reversed oxidative histological and immunological alterations caused by EAE. CONCLUSIONS: In conclusion, the GA treatment can protect the brain tissue against EAE in mice with its antioxidant and anti-inflammatory properties.

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats

Abstract Purpose: To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyclophosphamide side effects. Methods: A 40 healthy adult female Wistar albino rats were used in this study. Rats were randomly divided into four groups to determine the effects of curcumin and capsaicin against Cyclophosphamide side effects on the uterus (n=10 in each group); Group 1 was the control group (sham-operated), Group 2 was the cyclophosphamide group, Group 3 was the cyclophosphamide + curcumin (100mg/kg) group, and Group 4 was the cyclophosphamide + capsaicin (0.5 mg/kg) group. Results: Increased tissue oxidative stress and histological damage in the rat uterus were demonstrated due to the treatment of systemic cyclophosphamide chemotherapy alone. The level of tissue oxidant and antioxidant markers and histopathological changes were improved by the treatment of curcumin and capsaicin. Conclusion: Cytotoxic effects of natural alkylating chemotherapeutic agents like cyclophosphamide on the uterus can be prevented by curcumin and capsaicin.

Curcumin protects heart tissue against irinotecan-induced damage in terms of cytokine level alterations, oxidative stress, and histological damage in rats.

Irinotecan (CPT-11), commonly used in the treatment of many cancer types, may have several side effects that limit the use of CPT-11 in specific tissues such as the heart. In the current study, positive effects of curcumin (CRC) was determined in terms of antioxidant and anti-inflammatory properties against heart damage, caused by CPT-11, in rats. Rats were divided randomly into four equal groups (Control, CPT-11, CRC, and CPT-11 + CRC). CPT-11 10 mg/kg/day was administered intraperitoneally and CRC 100 mg/kg-1 was given orally. Blood and tissue samples were collected from all groups at day 30 for the detection of oxidative stress, histological changes, and cytokine levels. Results showed that CPT-11 caused dramatic changes in heart tissue for oxidative stress parameters (TBARS, SOD, CAT, GSH, and GPx levels), histological tissue damage, and cytokine levels (TNF and IL-4). CRC therapy reversed the elevated oxidative stress, histological tissue damages, and immunological changes and protected cardiac tissue against CPT-11 toxicity when given together with CPT-11.In conclusion, CPT-11 caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, CRC treatment eliminated these toxic effects with its antioxidant and anti-inflammatory properties. Thus, these results suggest that CRC may play a protective role against CPT-11 toxicity in heart tissue of rats.

The beneficial effects of nerolidol and hesperidin on surgically induced endometriosis in a rat model.

The objective of this article is to analyze the effects of nerolidol and hesperidin treatment on surgically induced endometriosis in a rat model. Endometriosis was induced in 24 healthy adult female Wistar albino rats via homologous uterine horn transplantation. Three operations were performed on each rat. After the second operation, the rats were randomized into control, nerolidol, and hesperidin treatment groups, and medications were administered for 2 weeks. The effects of the drugs on the endometriotic foci were evaluated after the third operation. Compared with the endometriosis control group, the average volume of the lesions was significantly lower in rats treated with hesperidin and nerolidol. Malondialdehyde levels were significantly reduced in the nerolidol-treated group, and glutathione levels and superoxide dismutase activity were significantly elevated in the endometriotic foci of both the hesperidin- and nerolidol-treated groups compared with the endometriosis group. Hesperidin and nerolidol treatment also improved histological parameters, such as hemorrhage, vascular congestion, necrosis, and inflammatory cell infiltration in the endometriotic foci. The results of this study demonstrated that treatment with the potent antioxidants nerolidol and hesperidin caused a significant regression of surgically induced endometriotic foci in rats.

Hesperidin, a Citrus Flavonoid, Has the Ameliorative Effects Against Experimental Autoimmune Encephalomyelitis (EAE) in a C57BL/J6 Mouse Model.

The aim of this study was determined the effects of Hesperidin (HP) on neuronal damage in brain tissue caused by Experimental allergic encephalomyelitis (EAE), an established model of multiple sclerosis in C57BL/J6 mice. To explore 40 mice were equally divided into four groups: (1) Control, (2) EAE, (3) HP, and (4) HP + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, the mice treated with HP at the doses of 50 mg/kg/day for 7 days subcutaneously. To our results HP treatment prevents the oxidative stress caused by EAE via a decrease in lipid peroxidations and increase in elements of the antioxidant defense systems in brain tissue. Also, EAE elevate the IL-17, express the pro-inflammatory cytokines, and caspase-3-like immunreactivity, show apoptosis, staining in EAE mice brain and increased the incidence of histopathological damage. However, immonohistochemical and histological changes were reversed with HP. Moreover, elevated TNF-α and IL-1ß levels, a result of EAE, were decreased in serum and neurological deficits as clinical signs were reversed with HP treatment in EAE mice, given HP. In conclusion, HP treatment effectively prevents oxidative, immunological and histological damage in the brain caused by EAE. It was thought that the beneficial effects of HP are likely a result of its strong antioxidant and anti-inflammatory properties.

The beneficial effects of 18ß-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model.

This study investigated the effects of 18ß-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.

Antioxidative effects of curcumin, ß-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver.

The aim of this study was to investigate the effectiveness of curcumin, ß-myrcene (myrcene) and 1,8-cineole (cineole) on antioxidant defense system in rats given a persistent environmental pollutant (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD). Rats (n = 112) were divided randomly into 8 equal groups. One group was kept as control and given corn oil as carrier. TCDD was orally administered at the dose of 2 µg/kg/week. Curcumin, myrcene and cineole were orally administered at the doses of 100 mg/kg/day, 200 mg/kg/day and 100 mg/kg/ day, respectively, by gavages dissolved in corn oil with and without TCDD. The liver samples were taken from half of all rats on day 30 and from the remaining half on day 60 for the determination of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and CuZn-SOD levels by spectrophotometric method. The results indicated that although TCDD significantly (p ≤ 0.01) increased formation of TBARS, it caused a significant decline in the levels of GSH, CAT, GSH-Px and CuZn-SOD in rats. In contrast, curcumin, myrcene and cineole significantly increased GSH, CAT, GSH-Px and CuZn-SOD levels but decreased formation of TBARS. Additionally, the antioxidative effects of curcumin, myrcene and cineole were increased at day 60 compared to day 30. In the TCDD groups given curcumin, myrcene and cineole, oxidative stress decreased by time. In conclusion, curcumin, myrcene and cineole showed antioxidant activity and eliminated TCDD-induced oxidative stress in rats in a time-dependent manner.