Effect of Uric Acid on Gentamicin‐Induced Nephrotoxicity in Rats – Role of Matrix Metalloproteinases 2 and 9

Abstract

In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.

Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model

“…Especially, the perifilamentary MMP-2 expression was significantly diminished by mesh coating with a concentration of 8 μg/mg gentamicin at each time point. The effect of gentamicin on MMP-2 expression was likewise investigated in previous studies, but in contrast to these results, our findings demonstrate a presumably dose-dependent downregulation of the MMP-2 for the first time [21,46]. Such a dose-dependent effect of gentamicin is supported by the finding that the administration of gentamicin in nephrotoxic doses induces MMP-2 expression [47].…”

Thymoquinone Ameliorates Acute Renal Failure in Gentamicin-Treated Adult Male Rats

“…TQ supplementation after GEN injection reversed the decreased blood Cr, urea and lipid peroxides [26]. In agreement with other literatures, this work showed that GEN increases MDA level as an end product of lipid peroxidation and decreases the levels and activities of GSH, SOD and GPx [27]. Decreased lipid peroxidation and increased SOD and GPx activities after administration of TQ suggest that TQ ameliorates its antioxidant properties by scavenging the free radicals [28].…”

Protective Effect of Carvacrol on Renal Functional and Histopathological Changes in Gentamicin-Induced-Nephrotoxicity in Rats

“…Gentamicininduced-nephrotoxicity can cause renal injuries due to ROS generation [4,14,15]. Antioxidant compounds such as melatonin [27], vitamin E and probacol [28] etc.…”

“…Thus; they are more sensitive to reactive oxygen species (ROS) effects. Gentamicin-induced nephrotoxicity increases the level of serum creatinine and urea, tubular necrosis and glomerular congestion but decrease glomerular filtration rate [13][14][15]. In studies done on antioxidant compounds such as curcumin [16] olive leaf extract [5], green tea and coenzyme Q10 [6] and rosmarinic acid [17] such as antioxidant compounds played effective roles in reduction or decrease of renal injuries caused by using of gentamicin.…”