Rhizoma smilacis glabrae protects rats with gentamicin-induced kidney injury from oxidative stress-induced apoptosis by inhibiting caspase-3 activation

Abstract

Ethnopharmacological relevance: Rhizoma smilacis glabrae (RSG), which is mild-natured and tastes sweet or bland, has pharmacological action of eliminating dampness, detoxifying, and ensuring that joints were healthy and supple in traditional Chinese medicine.

Aim of the study: To discuss the protective effect of RSG on gentamicin (GM)-induced kidney injury in rats and its regulatory mechanisms of oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

Materials and methods: A total of 40 Sprague-Dawley (SD) rats were randomly divided into 5 groups: control group, model group, and RSG low, middle, and high dose groups (0.75，1.5，3gkg^-1). Six hours after intramuscular GM injections, rats in the model group were given distilled water by intragastric administration, and rats in the 3 RSG intervention groups were given different dosages of RSG water-extracts. Twenty-four hours after the last administration, blood and kidney samples were collected to test for biochemical indexes of kidney injury, oxidative stress, histopathological defects, apoptosis rate, and caspase-3 protein expression to assess the protective effect of RSG water-extracts against GM-induced kidney injury.

Results: Compared with the model group, serum TP and ALB levels were significantly higher (P<0.05), and BUN, CRE, and UA levels were significantly lower (P<0.05) in the 3 RSG intervention groups. In kidney tissues, SOD, CAT, and GSH levels increased significantly (P<0.05), while MDA level decreased significantly (P<0.05). Total apoptosis rate dropped markedly (P<0.01), and the protein expressions of caspase-3 increased, while expressions of activated caspase-3 decreased. Histopathological analysis showed shrinkage of kidney cells reduced with appearance of complete kidney structure and decrease in activated caspase-3 expressions in impaired renal tubules decreased. Among the 3 RSG intervention groups, the middle dose group (1.5gkg^-1) showed the best protective effect.

Conclusions: RSG water-extracts had protective effects against GM-induced kidney injury in rats, and its mechanism of action was related to oxidative stress-induced apoptosis by inhibiting caspase-3 activation.

Keywords: Apoptosis; Caspase-3; Kidney injury; Oxidative stress; Rhizoma smilacis glabrae water-extracts.