Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice.

PURPOSE: Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. METHODS: Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1ß) levels as inflammatory mediators were assessed in kidney tissue. RESULTS: The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1ß and increasing the level of GSH, CAT, SOD, and GPx activities. CONCLUSION: Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats.

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

Ellagic Acid Prevents Oxidative Stress, Inflammation, and Histopathological Alterations in Acrylamide-Induced Hepatotoxicity in Wistar Rats.

The present study was designed to investigate the changes in rat liver tissue after administration of acrylamide (ACR) and ellagic acid (EA). The latter compound was applied for its strong antioxidant and anti-inflammatory properties. In the present study, 35 male Wistar rats were randomly divided into five equal groups. These groups were normal saline (NS), ACR (20 mg/kg), ACR + EA (10 and 30 mg/kg EA), and EA (30 mg/kg). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on liver and serum samples. ACR administration significantly decreased hepatic GSH level, SOD, GPx, and CAT activity when compared to the NS group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1ß) levels increased as a result of ACR administration. Administration of EA (more potently at a dose of 30 mg/kg) resulted in a significant reversal of biochemical, inflammatory, and hepatic markers in ACR-intoxicated rats. These biochemical and inflammatory disturbances were supported by histopathological observations of the liver. Our results indicate that EA might be useful for the treatment of the hepatotoxicity induced by ACR via ameliorative effects on biochemical, oxidative stress, and inflammatory indices.

Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats.

Acrylamide (ACR) is an environmental contaminant and a well-known neurotoxin. Ellagic acid (EA), a natural plant polyphenol, has shown a variety of beneficial effects. The present study was designed to explore whether EA could attenuate ACR-induced neurotoxicity in rats and to explore the underlying mechanisms. Animals were divided into five groups. Group 1 was treated with normal saline (2 mL/kg) for 30 days. Group 2 was treated with ACR (20 mg/kg, orally) for 30 days. Groups 3 and 4 were treated with ACR and EA (10 and 30 mg/kg, orally) for 30 days. Group 5 was treated with EA (30 mg/kg, orally) for 30 days. Open field, rotarod and passive avoidance test were conducted to evaluate behavioral changes, respectively. The brain cortex was used for histological examination. Different oxidative parameters and inflammatory biomarkers were assessed in the brain cortex. ACR-administered rats showed a considerable impairment in exploratory behavior, motor performance as well as cognition. Our data also showed that ACR administration significantly increases malondialdehyde, nitric oxide, interleukin-1ß and tumor necrosis factor-α levels. Moreover, it decreases brain glutathione level, superoxide dismutase, glutathione peroxidase, catalase activity. Co-administration of EA (especially 30 mg/kg, p.o.) prevented these changes; however, it did not affect the glutathione peroxidase activity. These results were supported by histopathological observations of the brain. Our results suggest that EA can be useful for protecting brain tissue against ACR-induced neurotoxicity through ameliorative effects on inflammatory indices and oxidative stress parameters.