Mandarin peel ethanolic extract attenuates diclofenac sodium induced hepatorenal toxicity in rats by mitigating oxidative stress and inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute approximately one-third of the global pharmaceutical market and are the first drugs of choice when treating fever and pain. Furthermore, among NSAIDs, the use of diclofenac sodium (DS) is preferred as it is a strong inhibitor of cyclooxygenase enzyme. However, despite its strong efficacy, DS is known for its potential to cause hepatorenal damage. Currently, to mitigate the adverse effects of certain drugs, medically effective agricultural products are often preferred as they are inexpensive, effective and safe. One such agricultural product-mandarin-is noteworthy for its high phenolic contents. The purpose of the present study was to assess the efficacy of mandarin peel ethanolic extract (MPEE) in protecting against hepatorenal damage induced by DS. Four groups (six/group) of adult male albino rats received oral administration of physiological saline (control group), DS (10 mg/kg body weight), MPEE (200 mg/kg body weight), and DS + MPEE for 7 days. Rats in the DS group showed increased serum levels of ALT, AST, ALP, BUN, CRE, and UA. Furthermore, the hepatic and renal tissue levels of MDA, TNF-α and IL-1ß increased, whereas those of GSH, SOD, GP-x and IL-10 decreased (p < 0.05). Investigation of MPEE in terms of its effects on biochemical, oxidative and inflammatory parameters, it exerted protective and healing effects. Therefore, MPEE can be used to ameliorate DS-induced hepatorenal damage.

The protective effects of erdosteine on subacute diazinon-induced oxidative stress and inflammation in rats.

In today's world, pesticides are commonly used to control pests and in advanced agriculture. As an organophosphorus insecticide (OPI), diazinon (DZN) is a commonly used substance. However, the widespread usage of DZN increases the probability of incidence of toxication. This toxication has been reported to be shaped not through cholinergic syndromes that are experienced as a result of acetylcholinesterase inhibition, which is the primary effect of these cases. It is rather shaped by the altering of the facilitation of oxidative stress and inflammatory response. In this study, the protective effect of administering erdosteine (ERDOS) subacute DZN exposure was investigated. A total of 24 male Wistar albino rats were separated into 4 groups (with 6 rats in each group), namely, the control, DZN (15 mg/kg/day), ERDOS (10 mg/kg/day), and DZN + ERDOS (15 mg/kg/day DZN + 10 mg/kg/day ERDOS) groups. These medications were given through oral gavage for 28 days. With the whole blood, plasma, and serum samples taken from the rats, oxidant-antioxidant parameters and cytokine levels were measured. The MDA and NOx levels and SOD and CAT enzyme activities of the DZN group were higher than those of the control group, while the GSH levels and TAC and GPx activities of the DZN group were lower than those of the control group (p < 0.05). It was also found that cytokine (IL-1ß, IL-10, and TNF-α) levels in the DZN group were higher than those in the control group (p < 0.05). On the other hand, the ERDOS implementations were detected to ameliorate the harmful effects of DZN on the oxidant-antioxidant parameters and cytokine levels (p < 0.05). Conclusively, besides the known mucolytic efficacy of ERDOS, it may also be stated to display free radical scavenger, antioxidant, and anti-inflammatory characteristics to inhibit some proinflammatory cytokines that are specifically involved in oxidative stress. Additionally, the ameliorating property of ERDOS can be benefited from in possible DZN-induced toxication cases.

Protective effects of resveratrol on biomarkers of oxidative stress, biochemical and histopathological changes induced by sub-chronic oral glyphosate-based herbicide in rats.

The aim of this sub-chronic toxicity study is to determine the protective effects of Resveratrol (Res) on oxidative stress, biochemical and histopathological changes induced by glyphosate-based herbicide (GBH) in the blood, brain, heart, liver and renal tissues. A total of 28 male Wistar rats were equally divided into 4 groups so that each group included 7 rats. In the study, Group I (control group) was given normal rodent feed and tap water ad libitum. Group II (Res group) was given Res 20 mg kg-1, Group III (GBH group) was given GBH of 375 mg kg-1 to achieve 1/10 of Lethal Dose 50% (LD50), and Group IV (Res + GBH) was given Res 20 mg kg-1 and GBH 375 mg kg-1 with oral gavage once a day for 8 weeks. While GBH decreased the glutathione (GSH) levels in the blood, brain, heart, liver and renal tissues, it significantly increased malondialdehyde (MDA) levels. In contrast, the aforementioned parameters were seen to recover in the group to which Res was administered. Moreover, it was observed that Res improved the histopathological changes induced by GBH in rat tissues. In conclusion, Res prevents oxidative stress caused by GBH by preventing lipid peroxidation (LPO) and boosting the antioxidant defense system and decreases the damage in the brain, heart, liver and renal tissues of Wistar rats.

Antioxidant and cytoprotective effects of N-acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats.

It is claimed that oxidative stress has a prominent role in the mechanism of toxic effects formed by glyphosate-based herbicide (GBH) in living systems. A strong thiol compound, N-acetylcysteine (NAC), has antioxidative and cytoprotective properties. The objective in this subchronic toxicity study was to identify the prophylactic effect of NAC over histopathological changes and oxidative stress induced by GBH in blood, renal, liver, cardiac, and brain tissues. A sum of 28 male Wistar rats were divided into four equal groups, each containing 7 rats. During the study, group I (control group) was supplied with normal rodent bait and tap water ad libitum. The applied agents were 160 mg/kg NAC to group II, 375 mg/kg as equivalent to 1/10 of lethal dose 50% (LD50) of GBH to group III, and 160 mg/kg of NAC and 375 mg/kg of GBH together once per day as oral gavage to group IV for 8 weeks. While GBH decreased the levels of GSH in blood, liver, kidney, and brain tissues, it considerably increased malondialdehyde levels. On the contrary, these parameters happened to improve in the group supplied with NAC. Besides, it was seen that NAC was observed to improve the histopathologic changes in rat tissues induced by GBH. It was concluded that NAC protects oxidative stress and tissue damage induced by GBH in blood and tissue and this prophylactic effect could be attributed to its antioxidant and free radical sweeper character.

The roles of melatonin and vitamin E plus selenium in prevention of oxidative stress induced by naloxone-precipitated withdrawal in heroin-addicted rats.

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Beneficial effect of N-acetylcysteine against organophosphate toxicity in mice.

Recent studies showed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compounds toxicity. The aim of present study was to investigate either prophylactic and therapeutic effects of N-acetylcysteine (NAC) against fenthion-induced oxidative stress in mice. Additionally, the effects on survival rates were investigated. Therefore, we determined the changes of the blood levels of glutathione (GSH), malondialdehyde (MDA), nitrite, and nitrate in blood or serum. Additionally, all animals were observed for 6 h and the survival rates were recorded. It was found that fenthion administration increased the levels of MDA, and decreased the levels of GSH, nitrite and nitrate. On the other hand, both prophylactic and therapeutic NAC treatment decreased the levels of MDA, and increased the levels of GSH, nitrite, and nitrate. The results showed that NAC is able to attenuate the fenthion-induced oxidative stress whereby NAC has not only prophylactic but also therapeutic activity in fenthion poisoning. On the other hand, we found that NAC can clearly improve survival rates in mice administered with an acute high dose of fenthion poisoning. In conclusion, NAC can decrease OP-induced oxidative stress and mortality rate, but the exact mechanism of its NAC protective effect needs to be explored further.

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats.

AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs 13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Effects of aminoglycoside antibiotics on renal antioxidants, malondialdehyde levels, and some serum biochemical parameters.

Effects of amikacin, gentamicin, kanamycin, and streptomycin on renal tissue superoxide dismutase, glutathione peroxidase, glutathione and malondialdehyde, serum creatinine, potassium, sodium, total protein, glucose, uric acid, and total bilirubin levels were investigated. All aminoglycoside antibiotics decreased renal tissue glutathione levels.