Background. Taurine, which is the major intracellular free β‐amino acid, is known to be an endogenous antioxidant and a membrane‐stabilizing agent. In this study, we wished to know whether taurine altered the concentration of gentamicin in kidney tissue and could protect against gentamicin‐induced acute proximal tubular injury. Methods. Wistar albino rats of both sexes were assigned to three groups, which all received one of the following daily intraperitoneal injections for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus 7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was collected for 24 h for the determination of urine volume and creatinine. Intracardiac blood was collected for blood urea nitrogen (BUN) and serum creatinine determination. The kidneys were removed, weighed, and the left kidneys were subjected to biochemical analysis for the determination of thiobarbituric acid‐reactive substance (TBARS) and lactate levels, and glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided vertically in half. The upper halves were used for histopathological examination, by light and electron microscopy. The lower halves were used to detect the gentamicin concentration within the kidney tissue, by high‐performance liquid chromatography (HPLC). Changes in body weight and normalized kidney weight were recorded. Results. Taurine treatment reduced gentamicin‐induced increases in serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels (0.57±0.02 vs 1.06±0.08 mg/dl, P<0.001; 9.00±1.46 vs 20.9±2.73 ml, P<0.001; 25.3±1.87 vs 54.1±6.99 mg/dl, P<0.001; 2.56±0.10 vs 3.44±0.08 μmol/g wet tissue, P0.05, respectively). Taurine reduced the accumulation of gentamicin within the kidney tissue (233±29 vs 494±93 μg/g wet tissue, P<0.05). Taurine treatment also prevented body weight loss due to gentamicin administration (17.8±1.64 vs −10.0±7.08 g, P<0.01) and normalized reduced Gpx and SOD activities (3.46±0.16 vs 2.37±0.15 U/g wet tissue, P<0.01; and 15577±377 vs 12662±577 U/g wet tissue, P<0.01, respectively). Light microscopic examination of the renal tissues from gentamicin‐treated rats revealed severe histopathological changes, whereas specimens obtained from taurine‐treated rats revealed only mild changes. This finding was supported by electron microscopic examination. Conclusions. Our observations suggest that taurine treatment attenuates the accumulation of gentamicin within kidney tissue and counteracts the deleterious effect of gentamicin on renal tubular function. They may have potentially important clinical implications.

Background: Gingival enlargement is one of the side effects associated with the administration of phenytoin. The mechanism by which phenytoin induces gingival enlargement is not well understood. This study was conducted to investigate the relationship between plasma and gingival crevicular fluid (GCF) phenytoin concentrations and the degree of gingival overgrowth in patients with similar gingival and plaque indices and also to determine the risk factors for gingival enlargement.Methods: Eighteen patients taking phenytoin in regular doses ≥6 months prior to the investigation participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. The gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD), and clinical attachment level (CAL) were also evaluated. GCF and plasma phenytoin concentrations were determined by using high‐performance liquid chromatography (HPLC).Results: There was no significant difference between responders and non‐responders for PD, CAL, PI, GI, and GBTI. Phenytoin was detected in all of the GCF and plasma samples using the HPLC analysis method. The mean concentration of phenytoin in GCF was significantly greater than the concentration of phenytoin in plasma. No significant difference was observed for the concentration of GCF phenytoin between responders and non‐responders. However, the concentration of plasma phenytoin was significantly higher in responders than non‐responders.Conclusion: This study showed that plasma phenytoin level appeared to be a risk factor for phenytoin‐induced gingival overgrowth.

Cyclophosphamide (CPA) and adriamycin (ADR) are widely used drugs for cancer chemotherapy. It has been reported that CPA and ADR singly or in combination could alter activities of a variety of drug-metabolizing enzymes in animals via multiple mechanisms. However, the effects of CPA/ADR on drug metabolism are largely unknown in human beings. Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO). The present study was designed to analyze the effects of CPA/ADR on these drug-metabolizing enzymes by using losartan and caffeine as probe drugs. A single oral dose of 25 mg losartan and a cup of instant coffee was given to 15 breast cancer patients on three occasions (before, and 2-4 h and 3 weeks after the adjuvant CPA/ADR chemotherapy [600 mg CPA/m2/day, 60 mg ADR/m2/day]). Losartan, caffeine and their metabolites were analyzed by using high-pressure liquid chromatography. When compared with baseline, CYP1A2 activity was increased by 20% and CYP2C9 activity was decreased by 315% 3 weeks after the administration of CPA/ADR chemotherapy (p = 0.05). The chemotherapy did not change the activities of CYP2A6, NAT2 or XO. CPA/ADR treatment caused a differential effect on drug-metabolizing enzyme activities, and this may contribute to predicting the efficacy and toxicity of chemotherapeutics, as well as understanding the drug-drug interactions.