Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats

Abstract

This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX-induced nephrotoxicity that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.

Toxicological Profile of the Pain-Relieving Antioxidant Compound Thioctic Acid in Its Racemic and Enantiomeric Forms

“…Being both administrations toxic, (−) enantiomer appeared to be the responsible for the results induced by racemic mixture. In literature we found voices opposing to our results: some studies reported an antiapoptotic activity of thioctic acid, when the dietary supplement was administered orally and at lower concentration (50 mg/kg) [ 29 , 30 ].…”

Yiqi Fumai lyophilized injection attenuates doxorubicin-induced cardiotoxicity, hepatotoxicity and nephrotoxicity in rats by inhibition of oxidative stress, inflammation and apoptosis

“…Researchers demonstrated that elevation of apoptosis-related protein like BAX, caspase-3 and cytochrome c in DOX-intoxicated rats might be contributed to renal dysfunction. 54,58 By activating caspase-3 in renal proximal tubular cells and causing mitochondrial pathway, DOX probably leads apoptosis, which can arise renal cell damage and disorganized renal histology. 59 In present study, under the pretreatment of YQFM, expressions of BAX/Bcl-2 ratio, caspase-3 and cytochrome c were quite reduced, and then the inhibition of apoptosis could prevent tissue lesions and dysfunction, which was associated to the effect of ginsenosides included in YQFM.…”

Renoprotective Effect of Plantago major Against Proteinuria and Apoptosis Induced by Adriamycin in Rat

“…It has been demonstrated that proteinuria is caused by glomerulosclerosis and loss of glomerular podocytes due to cell death/apoptosis [ 1 ]. Results from previous studies have demonstrated that oxidative stress, inflammation, and apoptosis are involved in the development of NS pathological features [ 2 ]. In the patients without effective treatment, NS leads to end-stage renal disease (ESRD) and require renal transplantation [ 1 ].…”

“…Despite the advances in NS studies in recent decades, the pathophysiology of this disease remains unknown and more studies are needed to clarify its exact pathophysiological mechanisms. Adriamycin (ADR) is a common anticancer drug that has been used for the treatment of a wide range of human solid tumors since 1969 [ 2 ]. However, despite having high antitumor efficacy, its effectiveness has been limited, because of renal, myocardia, testicular, and hematological toxicities [ 3 ].…”

“…The overproduction of ROS and imbalance between free oxygen radicals and antioxidants could trigger the immune response and mediate inflammation. Inflammatory mediators and cytokines play an important role in ADR-induced renal injury including increase glomerular capillary permeability as well as tubular atrophy and apoptosis [ 2 , 9 ]. The use of antioxidant compounds can be beneficial for nephrotoxicity caused by ADR.…”