Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats

Background

Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.

Methods

We administered recombinant human IGF-I (rhIGF-I, 150 µg/day, i.p.) once a day 24 h prior to and after CDDP (5 mg/kg, i.v.) injection in rats.

Results

The rhIGF-I treatment significantly decreased serum creatinine (0.92 ± 0.11 vs 1.50 ± 0.15 mg/dl; P ≪ 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 (P ≪ 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 ± 0.19 vs 3.45 ± 0.42/×400 high-power field (HPF); P ≪ 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 ± 1.89 vs 18.26 ± 2.14/×400 HPF; P ≪ 0.05), but decreased the number of cyclin D1-positive cells (3.3 ± 0.3 vs 6.3 ± 1.7/×400 HPF; P ≪ 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.

Conclusions

Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase.