Effect of silymarin on cisplatin-induced renal tubular injuries in adult male rabbits: a histological, immunohistochemical, and electron microscopic study

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Abstract

Background

Organ toxicity is a sophisticated medical problem encountered during treatment with antineoplastic agents. Cisplatin is a platinum compound effectively used as an anticancer drug. The flavonoid silymarin has been shown previously to be protective in many models of tissue toxicity.

Aim of the work

The aim of the present study was to evaluate the effect of silymarin on cisplatin-induced renal tubular injuries in rabbits.

Materials and methods

In this study, 20 adult male rabbits were used and divided equally into four groups. The first group served as the control group; the second was the cisplatin group (single intraperitoneal dose 5 mg/kg body weight); the third was the prophylactic silymarin group, which was given three oral doses of silymarin daily (52 mg/kg body weight/day) for 3 days before a single intraperitoneal dose of cisplatin; and the fourth was the curative silymarin group, which was given three oral doses of silymarin daily started 2 days after a single intraperitoneal dose of cisplatin. Kidney samples were taken 5 days after cisplatin injection. Paraffin sections were prepared for LM examination (H&E) and immunohistochemical detection of caspase-3, and ultrathin sections were prepared for electron microscopic examination. The mean area percentage of caspase-3 expression was measured in all groups, and statistical analysis was carried out.

Results

The results revealed that a single dose of cisplatin induced extensive vacuolization of the cell cytoplasm of renal tubules (proximal and distal) with tubular dilatation, cell apoptosis (highly expressed caspase-3), loss of apical microvilli with widened intercellular space of proximal tubules, and disorganization of basal infoldings with dispersed and degenerated mitochondria in the distal tubules. In the silymarin prophylactic group, it showed minimal vacuolization of tubular cell cytoplasm and minimally expressed caspase-3. In the silymarin curative group, it showed moderate cytoplasmic vacuolization of the renal tubular cells with slight tubular dilatation, moderately expressed caspase-3, few apical microvilli in proximal tubules, and disorganization of basal infoldings with dispersed and degenerated mitochondria in the distal tubules. Statistical analysis for caspase-3 expression revealed a significant decrease (P < 0.05) in caspase-3 expression in groups III and IV compared with group II.

Conclusion

It could be concluded that silymarin when used as a prophylactic agent was more effective in protection against cisplatin nephrotoxicity than when used as a curative agent and may be considered as a potentially useful candidate in combination chemotherapy with cisplatin.

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