Protective Effect of Tetrahydrocurcumin against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Abstract

The adverse effects of anticancer drugs can prompt patients to end their treatment despite the efficacy. Cisplatin is a platinum-based molecule widely used to treat various forms of cancer, but frequent and long-term use of cisplatin is limited due to severe nephrotoxicity. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin on cisplatin-induced kidney damage, oxidative stress, and inflammation to evaluate its possible use in renal damage. Cisplatin-induced LLC-PK1 renal cell damage was significantly reduced by tetrahydrocurcumin treatment. Additionally, the protective effect of tetrahydrocurcumin on cisplatin-induced oxidative renal damage was investigated in rats. Tetrahydrocurcumin was orally administered every day at a dose of 80?mg/kg body weight for ten days, and a single dose of cisplatin was administered intraperitoneally (7.5?mg/kg body weight) in 0.9?% saline on day four. The creatinine clearance levels, which were markers of renal dysfunction, in cisplatin-treated rats were recovered nearly back to normal levels after administration of tetrahydrocurcumin. Moreover, tetrahydrocurcumin exhibited protective effects against cisplatin-induced oxidative renal damage in rats by inhibiting cyclooxygenase-2 and caspase-3 activation. These results collectively provide therapeutic evidence that tetrahydrocurcumin ameliorates renal damage by regulating inflammation and apoptosis.

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate

“…Moreover, several pharmacological agents demonstrated anti-apoptotic effects by inhibiting Bax activation and accumulation in mitochondria. 24,25,29 In addition, our present work has further demonstrated compelling evidence for tubular apoptosis via inhibition of formation of ROS and secretion of TNF-α, which are known to activate the extrinsic pathway of apoptosis through death receptors. Alternatively, death receptors can generate ROS and enhance cisplatininduced acute kidney injury.…”

“…18,24,25 Inside the tubular cells, cisplatin is aquated into a highly reactive electrophile, which rapidly reacts with thiol-containing molecules including glutathione. It also induces mitochondrial dysfunction and increases ROS production by disrupting the respiratory chain.…”

Dietary tetrahydrocurcumin reduces renal fibrosis and cardiac hypertrophy in 5/6 nephrectomized rats

“…39 The observed renoprotective effects in our study are consistent with reports from other rodent models whereby THC enhanced antioxidative activity of superoxide dismutase, catalase and glutathione peroxidase. 12,13,16 The net effect is decreased production of reactive oxygen species, with subsequent downregulation of the caspase-3 apoptosis pathway 40 and tissue fibrosis. THC has similarly been shown to decrease albuminuria and blunt rise in serum creatinine in rats with diabetic nephropathy.…”

Potential of Pure Phytoconstituents and Herbs in Protection of Drug Induced Nephrotoxicity

“…A study was carried out to check for the nephroprotective action of Tetrahydro-curcumin and it was reported showing anti-inflammatory properties and preventing cisplatininduced nephrotoxicity in addition with preventing the activities of certain enzymes such as caspase-3 and cyclooxygenase-2. 21 Most probably, due to its antioxidant potential it was found nephroprotective in nature.…”