Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats.

Valproic acid (VPA) is a broad-spectrum drug that is now widely used as an antiepileptic. Although VPA has positive therapeutic effects, it also causes various toxic effects in tissues. Curcumin, a natural antioxidant found in ginger, has antibacterial and antiinflammatory activity. In this study, the toxic effects of VPA on brain, kidney, and liver tissues and the protective activity of curcumin against these effects were investigated. In this study, male Wistar-Albino rats were used. Rats were divided into 4 groups control, VPA, CUR, and CUR + VPA. Rats were administered intraperitoneal VPA and CUR intragastrically. In the study, MDA, SOD, IL-6, and IL-18 levels were measured by the ELISA method in rats. It was observed that VPA triggered oxidative stress and inflammation in tissues, while CUR administration positively regulated these parameters. Studies also showed that VPA increased the expressions of TNF-α and NF-kB in tissues, but CUR administration downregulated these expressions The findings revealed that CUR protects by preventing the oxidative stress and inflammation caused by VPA in the tissues and may be an important agent in reducing the side effects of this drug used as an antiepileptic.

Evaluation of cytokines in protective effect of docosahexaenoic acid in experimental achilles tendinopathy rat model induced with type-1 collagenase.

BACKGROUND: We aimed to investigate the effectiveness of docosahexaenoic acid (DHA) as a treatment for Achilles tendinopathy (AT) induced with type-I collagenase in rats and compare it with collagen. METHODS: The AT model was induced with type I collagenase, and animals were randomly assigned to groups. Group 1:AT, Group 2: Collagen (7.2 mg/kg/day), Group 3:DHA (300 mg/kg/day), and Group 4:DHA (100 mg/kg/day). Right tendons of Group1 were used as a healthy control (HC). Oral treatments were applied for eight weeks. Serum tumor necrosis factor-alpha(TNF-α), matrix metalloproteinase-13 (MMP-13), and interleukin-1 beta(IL-1ß) concentrations were determined by ELISA. Tendon samples were taken for histopathological evaluation and examined immunohistochemically with antibodies specific for Col1A1, TNF-α, MMP-13, IL-1ß, and nitric oxide synthase-2(NOS-2). The ultimate tensile force (UTF) yield force(YF) and stiffness were measured by biomechanical assessments. RESULTS: UTF,YF and stiffness values were increased in all treatment groups compared to the AT control, a significant increase was found in Group 2 (p < 0.05). There was severe degeneration of tendon cells in the AT control. The tendon cells in samples from Groups 2-3 were less degraded, and this was statistically significant (p < 0.05). TNF-α, MMP-13, IL-1ß, and NOS-2 expressions were significantly higher in the AT control compared to the HC. In all treatment groups, their concentrations were lower than in the AT control. Serum TNF-α, MMP-13, and IL-1ß levels were lower in all treatment groups (Especially in Group3 (p < 0.001)) compared to Group1. CONCLUSION: The efficacy of high-dose DHA as a treatment for AT was investigated from biochemical, histopathological, and biomechanical perspectives. The results showed that DHA could be an alternative treatment compound to collagen.

Effect of betulinic acid administration on TLR-9/NF-κB /IL-18 levels in experimental liver injury

Background/aim: Acetaminophen (APAP), used in the composition of thousands of preparations, is the most commonly used analgesic and antipyretic drug. The present study aimed to investigate the potential protective effects of the betulinic acid (BA) treatment through an APAP-induced hepatotoxicity rat model, using inflammatory, biochemical, and histopathological parameters. Materials and methods: The study consisted of four groups: control group, APAP group, BA group, and APAP+BA group. Experimental studies continued for fifteen days. Serum samples were analysed for glucose, total cholesterol (TChol), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), aspartate amino transferase (AST), malondialdehyde (MDA), toll-like receptor-9 (TLR-9), nuclear factor kappa B (NF-κB), and interleukin-18 (IL-18). Results: TLR9, IL-18, NF-κB, and MDA levels increased significantly in liver injury groups. These increases considerably decreased by the BA treatment. All groups showed immunopositivity for 8-hydroxy-2'­deoxyguanosine (8-OHdG) and interleukin (IL-1ß) in the hepatocytes, inflammatory cells, and epithelial cells of bile ducts. Conclusion: BA can be used as an effective agent in the prevention and treatment of acute liver diseases due to its inhibitory properties in multiple pathways and its potent antioxidant effects.

Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes.

Objectives: Diabetes mellitus (DM) is an important public health problem all over the world, considering its complications and increasing prevalence. Oleanolic acid (OA) has anti-diabetic property via modulating glucose metabolism and acting as 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) / Sirtuin-1 (SIRT-1) activator and Interleukin 6 (IL-6) / Nuclear factor kappa B (NF-κB) inhibitor. This research questioned if the OA treatment amliorates the hepatic inflammatory profile in the diabetic rats. Methods: Twenty-eight male Sprague Dawley rats were first subjected to either no diabetes induction (healthy) or diabetes induction by i.p. injection of 50 mg/kg streptozotocin. Then rats in both groups were treated with either tap water or OA (5 mg/kg) within 1 ml tap water by oral gavage for 21 days. Results: The diabetic rats had higher hepatic MDA (2.88x) and serum AST (2.01x), ALP (2.22x), and ALT (4.27x) levels and 50% lower hepatic SOD level than the healthy rats. The OA treatment significantly reversed these antioxidant parameters in the diabetic rats. The diabetic rats had lower AMPK (85%) and hepatic SIRT-1 (47%) levels and higher hepatic NF-κB (53%) and IL-6 (34%) levels than the healthy rats. Comparing with the health rats, the OA treatment increased hepatic SIRT-1 level, but tended to increase hepatic AMPK level and decrease hepatic NF-κB and IL-6 levels in the diabetic rats. It was also partially effective to ameliorate degenerative changes and necrosis in the diabetic rats. Conclusion: The OA treatment can be considered to alleviate oxidative stress and reduce severity of inflammation in hepatocytes in the diabetic subjects.

Effects of oleanolic acid on inflammation and metabolism in diabetic rats.

Diabetes mellitus (DM) is a chronic metabolic disease that threatens the health of the world population. We investigated the effects of oleanolic acid (OA) administration on inflammation status and metabolic profile in streptozotocin (STZ) induced diabetic rats. Four experimental groups were established: healthy rats not administered OA, healthy rats administered OA, diabetic rats not administered OA, diabetic rats administered OA. OA, 5 mg/kg, was administered by oral gavage for 21 days. Serum samples collected at the end of the experiment and analyzed for toll-like receptor-9, interleukin-18, nuclear factor kappa B, malondialdehyde MDA, glucose, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, calcium, phosphorus, magnesium and potassium. Pancreas tissue was examined for pathology. Induction of DM caused increased serum concentrations of inflammation and oxidative damage markers. DM also caused hyperglycemia-hyperlipidemia and decreased serum concentration of minerals. The islets of Langerhans were degenerated and necrotic. Administration of OA reversed the adverse effects of DM. OA treatment can ameliorate inflammation and oxidative damage due to DM by normalizing hyperglycemia and decreasing TLR-9, IL-18, NF-κB and MDA levels.

Effects of high fructose diet on lipid metabolism and the hepatic NF-κB/ SIRT-1 pathway.

The liver is the primary site for fructose metabolism; therefore, the liver is susceptible to fructose related metabolic disturbances including metabolic insulin dysfunction, dyslipidemia and inflammation. We investigated whether astaxanthin (ASX) can modify hepatic nuclear factor-kappa B (NF-κB)/sirtuin-1 (SIRT-1) expression to alter oxidative stress caused by ingestion of excess fructose in rats. The animals were divided randomly into two x two factorially arranged groups: two regimens were given either water (W) or 30% fructose in drinking water (F). These two groups were divided further into two subgroups each: two treatments, either orally with 0.2 ml olive oil (OO) or 1 mg ASX/kg/day in 0.2 ml olive oil (ASX). Fructose administration increased serum glucose, triglycerides and very low density lipoproteins, and decreased serum concentration of high density lipoproteins; fructose did not alter serum total cholesterol. Excess fructose decreased hepatic superoxide dismutase (SOD) and increased hepatic NF-κB and MDA levels. ASX treatment increased hepatic SIRT-1 and decreased hepatic NF-κB and malondialdehyde (MDA) levels. ASX treatment decreased hepatic NF-κB and increased SOD levels, but did not alter MDA level in rats fed high fructose. ASX administration ameliorated oxidative stress caused by excess fructose by increasing hepatic NF-κB and SIRT-1 expression.

Astaxanthin alleviates renal damage of rats on high fructose diet through modulating NFκB/SIRT1 pathway and mitigating oxidative stress.

This study was conducted to determine the effect of astaxanthin (ASX) treatment on alleviation of renal damage in high fructose induced nephrotoxicity in rats. Treatments were arranged in a 2 × 2 factorial fashion: administrations of fructose (30%, via drinking water) and ASX (1 mg/kg/day, within 0.2 ml olive oil) for 8 weeks. Data were analyzed by two-way ANOVA. The ASX treatment decreased serum urea (p < .01) and blood urea-N concentrations (p < .02) at a lower extent in rats receiving fructose than those not receiving fructose. Moreover, the ASX treatment reversed the increases in malondialdehyde (MDA) (p < .0001) and nuclear factor kappa B (NF-κB) (p < .0003) levels and the decreases in superoxide dismutase (SOD) activity (p < .0001) and sirtuin-1 (SIRT1) level (p < .0004), in the kidney upon high fructose consumption. The data suggest that ASX supplementation alleviates renal damage induced by high fructose consumption through modulating NF-κB/SIRT1 pathway and mitigating oxidative stress.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.