Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals

Abstract

Cisplatin is a potent chemotherapeutic agent with a wide range of activities. Nephrotoxicity and cardiotoxicity represent it's major complication upon clinical use. The present study was carried out to evaluate the possible protective effect of DL-α-lipoic acid (LA) against cisplatin-induced nephrotoxicity and cardiotoxicity. Different groups of rats (n = 10) were administered either saline (control), cisplatin (10 mg/kg, i.p.), LA (100 mg/kg, i.p.) or their combination (LA 30 min prior to cisplatin administration). Twentyfour hours later all animals were decapitated and sera were used for estimation of activities of urea (BUN), creatinine (Cr), lactate dehydrogenase (LDH), and creatine kinase (CK). Homogenates of the kidney and heart were used for estimation of oxidative stress markers (reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO)). Additionally, caspase-3 activities and DNA-fragmentation were investigated in renal tissues. The results showed that cisplatin produced significant elevation in serum activities of LDH, CK, BUN, and Cr and also induced significant elevation in the oxidative stress makers (MDA and NO) accompanied by significant reduction in GSH and SOD in both kidney and heart. The integrity of DNA was heavily damaged and caspase-3 was activated in renal tissues. The results emphasized nephrotoxicty and cardiotoxicity of cisplatin. On the other hand, prior administration of LA significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters and protected both kidney and heart tissues. The histopathological examination emphasized the obtained results. In conclusion, LA is suggested to be a potential candidate to ameliorate cisplatininduced nephrotoxicity and cardiotoxicity without altering the antitumor efficacy of cisplatin.

Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells

“…Due to amphiphilic properties, ALA has more advantages compared with other antioxidants such as vitamin C and E. Interestingly, Lipoic acid and its reduced form, dihydrolipoic acid (DHLA) has a redox potential of −0.32 V while the redox potential of GSH/ GSSG is −0.24 V. This difference reflects the fact that ALA has a greater defense capacity against oxidative damage than does GSH and ALA is able to reduce oxidized glutathione to GSH (Dwivedi et al 2014;Gomes and Negrato 2014;Rochette et al 2013;Smith et al 2004). It displays antioxidant effects by scavenging ROS and regenerates other endogenous oxidized antioxidants to their active reduced form (Hussein et al 2012). Several studies have shown that ALA exert in models of disease characterized by an increase in oxidative stress, such as type 2 diabetes, Alzheimer and cardiovascular disease (Ahmed 2012;Henriksen 2006;Wollin and Jones 2003).…”

The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity

“…ALA may play a renoprotective role on cisplatin-induced nephrotoxicity through antioxidant and antiapoptotic mechanisms combined with the onset of mRNA expression of antioxidant genes. 26 In our study, SOD and CAT activities were significantly decreased in AK group compared with the control group; SOD and CAT activities were increased in ALA-treated group compared with AK group, but only CAT activity was statistically significant. There was no significant improvement in GPx activity.…”

“…The lower cellular infiltration and lower tissue damage in ALA treatment might be associated with its antioxidant properties. 9,26,27 These properties were important in its protective effect against oxidative renal damage.…”

“…[22][23][24] Nowadays, in several studies, antioxidant properties of ALA have been working mainly. 9,14,[25][26][27][28] In addition, ALA contains lipophilic and hydrophilic portions so it has lipophilic and hydrophilic properties, it also removes free radicals, regenerate other antioxidants, connect and facilitate the excretion of heavy metals. It stands out with all of these effects among other major antioxidants.…”

The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart

“…), hydrogen peroxide (H 2 O 2 ), Thiobarbituric Acid Reactive Substances (TBARS), and nitric oxide (NO) (15,16). Numerous studies reported that cisplatin has a potential to induce oxidative damage in heart tissue by causing peroxidation of the cell membrane and dysfunction of mitochondria (17,18).…”