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.

Thymoquinone ameliorates amikacin induced oxidative damage in rat brain tissue.

We investigated the potential neuroprotective effects of thymoquinone (TQ) on amikacin (AK) induced oxidative damage in rat brain. We used 21 male rats divided randomly into three equal groups. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% aqueous NaCl and given 1 ml 0.9% aqueous NaCl orally. The AK group was administered 1.2 g/kg aqueous AK i.p. as a single dose on the day 3 of the study. The AK + TQ group was given a single 1.2 g/kg dose of AK i.p. on the day 3 of the study plus 40 mg/kg/day TQ by oral gavage daily. Treatment with TQ increased serum ferritin and decreased serum calcium levels significantly. TQ also decreased NADPH oxidase-2, NADPH oxidase-4, and caspase-3 levels. Decreased malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and catalase (CAT) activities were detected in the AK + TQ group compared to the AK group. TQ administration inhibited lipid peroxide formation and blocked oxidative reactions, which reduced the MDA level and increased SOD and CAT activities induced by AK. Oxidative damage caused by AK was ameliorated by TQ treatment owing to its antioxidative and anti-apoptotic effects. TQ may be a potential therapeutic agent for reducing the severity of AK induced oxidative damage to the brain.

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.

Thymoquinone could be protective against valproic acid-induced testicular toxicity by antioxidant and anti-inflammatory mechanisms.

Although valproic acid (VPA) is a low-cost and effective drug, it is known to cause organ toxicity via oxidative stress and related process. In present study, we aimed to evaluate the possible protective effects of thymoquinone (TMQ) on VPA-induced testicular toxicity. Male Sprague-Dawley rats were divided into three as control, VPA (500 mg kg-1  day-1 ) for 14 days and VPA plus TMQ (50 mg kg-1  day-1 for 14 days) with seven rats in. Spermatic and interstitial degenerations induced by VPA were ameliorated with TMQ. In VPA group, increased TOS and OSI levels, and decreased TAS level were seen. TMQ reversed these oxidative stress parameters significantly. In Western analysis, VPA was found to increase the expressions of phospho-nuclear factor kappa beta (p-Nf-kB) and Caspase-3. These expressions were decreased by TMQ significantly. Intense immunostaining for p-Nf-kB, Caspase-3 and NADPH oxidase 2 induced by VPA were transformed to moderate immunostaining by TMQ. VPA-induced inflammation and apoptosis that were developed mainly by p-Nf-kB pathway were attenuated by TMQ. TMQ can be a candidate supportive treatment for patients who need long-term and high-dose VPA therapy. TMQ inhibits the Nf-kB activation, and in addition to antioxidant property, it shows anti-inflammatory feature on VPA-induced testicular toxicity.

The protective effect of resveratrol against risperidone-induced liver damage through an action on FAS gene expression.

The purpose of the study is to examine the protective effect of resveratrol on the fatty acid synthase gene expression against the side-effects of risperidone in an experimental model in rat liver. In this study, thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, RIS (2 mg/kg risperidone daily), RSV1 (2 mg/kg risperidone + 20 mg/kg resveratrol), RSV2 (2 mg/kg risperidone + 40 mg/kg resveratrol), and RSV3 group (2 mg/kg risperidone + 80 mg/kg resveratrol). On treatment day 15, liver tissue was taken for analysis. The resveratrol treatment significantly reduced weight gain as opposed to the risperidone administration. Moreover, the fatty acid synthase gene expression level increased significantly in RSV1 group (p = 0.011). In addition, resveratrol enhanced the total antioxidant status, high-density lipoprotein cholesterol levels and decreased alanine aminotransferase, aspartate aminotransferase, total cholesterol, gamma glutamyl transpeptidase, low density lipoprotein cholesterol, oxidative stress index, triglycerides, and total oxidant status levels significantly (p < 0.05). In conclusion, this study revealed that treatment with resveratrol might protect liver tissue against the side--effects of risperidone over fatty acid synthase gene expression. Resveratrol could be an effective course of therapy for enhancing therapeutic efficacy.

Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol.

OBJECTIVE: The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments. MATERIALS AND METHODS: Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n = 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n = 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n = 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n = 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. RESULTS: The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly (p < 0.05). CONCLUSION: This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats.

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban.

PURPOSE: The purpose of this study was to evaluate the cardiac and cerebral oxidative stress in the offspings of pregnant rats treated with oxytocin antagonist atosiban. METHODS: Experimentally naive, adult female Wistar-albino rats (200-250 g) were mated with adult male rats for copulation. After confirming pregnancy, eight gravid rats were then randomly assigned into two equal groups. The animals were treated from days 15 to 20 of gestation. One group acted as a control group, and received intraperitoneal (i.p.) injections of saline in a daily dose volume of 6 mg/kg/day. The second group received 6 mg/kg/day i.p. atosiban. On day 21 of gestation, pups were delivered by cesarean. The heart and brain tissues of the newborn rats were dissected and sent for the measurement of total oxidant status, total antioxitant status and oxidative stress index. RESULTS: There was no significant difference in birthweight or in the number of pups between two groups. Newborns from atosiban-treated mothers showed significantly increased oxidative stress in the plasma and heart tissue than that of controls which was confirmed by histological examination (P < 0.05). Oxidative stress parameters and histopathological results of the brain tissues of newborns were similar between two groups (P > 0.05). CONCLUSION: Oxytocin receptor blockage for the treatment of premature delivery may be associated with increased fetal morbidity and mortality secondary to the elevated oxidative stress in the heart of the newborns.

The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.