ABSTRACT
Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1ß) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chemical and Drug Induced Liver Injury/drug therapy , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Luteolin/pharmacology , Luteolin/therapeutic use , Methotrexate/toxicity , Animals , Antioxidant Response Elements/drug effects , Apoptosis/drug effects , Chemical and Drug Induced Liver Injury/physiopathology , Inflammation/chemically induced , Kidney/drug effects , Male , Oxidative Stress/drug effects , Protective Agents/pharmacology , RatsABSTRACT
Luteolin (LUT) is a glycosylated flavonoid compound that has multiple beneficial pharmacological and biological impacts. The current investigation was undertaken to evaluate the putative neuroprotective potency of LUT against neuronal damage induced by lead acetate (PbAc). Twenty-eight rats were placed into four equal groups. Group 1: served as the control group, group 2: rats were supplemented orally with LUT (50 mg kg-1), group 3: rats were intraperitoneally injected with PbAc (20 mg kg-1), and group 4: rats were pretreated with LUT before PbAc injection with the same doses. All animals were treated for 7 days. The exposure to PbAc increased the concentration of lead in the cortical tissue, neuronal lipid peroxidation, and nitric oxide (NO) production and decreased the antioxidant enzymes. Additionally, PbAc enhanced a neuroinflammatory response in the cortical tissue through increasing the pro-inflammatory cytokines secretion and inducible NO synthase expression. Moreover, cortical cell death was recorded following PbAc intoxication as evidenced by the enhancement of the proapoptotic and inhibiting the antiapoptotic markers. Interestingly, LUT supplementation reversed the cortical adverse reactions induced by PbAc. Taken together, these findings may suggest that LUT may be useful for attenuating neuronal damage induced by PbAc through inhibiting the oxidative damage, neuroinflammation, and the cortical cell death.
