Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg percent] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg percent], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

[Protective effect of Captopril and Allopunnol against renal warm ischemia reperfusion injury in dogs]

Captopril and Allopurinol have protective effect against renal warm ischemia with different mechanisms. The aime of this study was to evaluate this protective effect against induced 1 hour warm ischemia in dog's kidneys. This experimental study was done in the year 2006. We performed the operation on 15 healthy dogs. During these procedures both kidneys were clamped for 1 hour, then left kidney was removed for pathologic evaluation and right kidney remained insitue for functional assessment. Five random dogs received 1 [mg/kg]d[day] Captopril orally before and after surgery [captopril group]; another five dogs received 10 [mg/kg]/day Allopurinol orally before and after surgery [allopurinol group]. Five dogs of control group received no drugs. Serum urea and creatinine were measured preoperatively and on postoperative days of 1, 3, 5, 10 and 16 in all groups. Serum levels of urea and creatinine elevated in all groups but in Captopril group maximum levels of urea and creatinine were significantly lower than control [P<0.05]. In Allopurinol group the maximum rise of creatinine was significantly lower in comparison to control group [p< 0.05], but the maximum levels of urea in this group had no significant difference when compared with control values [p< 0.05]. There was no significant difference in pathologic changes in the three groups. One hour warm ischemia results in ATN so it is not safe for dog's kidneys. Althogh Captopril and Allopurinol do not prevent ATN after one hour warm ischemia; they can reduce its severity and improve renal function after warm ischemia