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  • br Discussion The aminoglycoside antibiotic gentamicin conti

    2021-10-12


    Discussion The aminoglycoside antibiotic gentamicin continues to be an important agent against life threatening infections. However, nephrotoxicity is a major complication of the gentamicin administration. Thus amelioration of nephrotoxicity would enhance its clinical use. Several approaches involving the use of chemical compounds have been used to reduce gentamicin nephrotoxicity (Ramsammy et al., 1986, Cuzzocrea et al., 2002, Parlakpinar et al., 2005). But little or no attention has been paid on the use of naturally occurring substances with potent antioxidant properties to protect against nephrotoxic damage induced by gentamicin. In the light of this, we have explored the possible protective role of curcumin, a natural antioxidant substance on gentamicin-induced oxidative stress. The results of the present study indicate that gentamicin administration brought about a significant increase in BUN, serum creatinine and decrease in creatinine Epirubicin HCl mg clearance. The results are in contrast with that of Guidet and Shah (1989) who did not observe any change in these parameters following treatment with gentamicin (100mg/kg/day) for 5 consecutive days. However, our data are in agreement with the reports of Shifow et al. (2000). The reason for this apparent inconsistency may be due to the duration of treatment with gentamicin. In our study, a dose of 100mg/kg/day gentamicin for 7 days was administered to rats as opposed to 5-day treatment in the study of Guidet and Shah (1989). Our results are in line with the observation that a decline in glomerular filtration rate and increase in serum creatinine and BUN are not usually apparent until 7 days of treatment with gentamicin (Humes and Wenberg, 1986). In this study, the apparent increase in urinary protein, glucosuria and increased urine output indicate proximal tubular dysfunction. The presence of tubular damage was further confirmed by increased urinary excretion of Epirubicin HCl mg marker gamma glutamyl transferase suggesting a direct toxic injury. Renal morphologic examination, which revealed the presence of tubular necrosis and proteinous casts further confirmed renal tubular damage. Reactive oxygen species including hydroxyl radical have been implicated in the aetiology of gentamicin-induced nephrotoxicity. Walker and Shah (1987) showed that gentamicin in vitro enhances the generation of hydrogen peroxide by renal cortical mitochondria and that iron chelators and hydroxyl-radical scavengers protect against gentamicin-mediated renal damage. Our results show that gentamicin-induced oxidative stress as demonstrated by significant elevation in lipid peroxidation and decreases in GSHPx and CAT activities. The depletion in GSH status might be responsible for the observed decrease in the activity of GSHPx. However, there was no difference in SOD activity in gentamicin-treated rats. The result is in agreement with the report of Pedraza-Chaverri et al. (2000) who observed that the activity of this enzyme was not affected in gentamicin-nephrotoxicity. Curcumin treatment significantly attenuated the gentamicin-mediated increase in, urinary protein and glucose, BUN, serum creatinine and decrease in creatinine clearance as well as the activity of gamma-glutamyl transferase. This effect may be related to the antioxidant properties of curcumin since it has been found that ROS may be involved in the impairment of glomerular filtration rate (Hughes et al., 1996). Similar antioxidants such as melatonin and Garlic have been shown to produce the same effect in gentamicin-treated rats (Sener et al., 2002, Pedraza-Chaverri et al., 2000). Furthermore curcumin prevented depletion of GSH, GSHPx and CAT activity induced by gentamicin treatment. The apparent protective effect might be due to the ability of curcumin to neutralize the increase in free radicals caused by gentamicin. The renoprotective effect of curcumin via scavenging of ROS is well documented. Curcumin has been shown to inhibit hydrogen peroxide-induced oxidative injury in a renal cell line (Cohly et al., 1998). Curcumin is also protective in adriamycin-induced renal injury and ferric nitrilotriacetate-induced oxidative renal damage (Venkatesan et al., 2000, Okada et al., 2001). Thus the preventive effect of curcumin on the gentamicin-induced decrease in the activity of GSHPx and CAT could contribute to the restoration of markers of renal tubular injury.