곰팡이 독소인 ochratoxin A(OA)는 신장독성, 최기형성, 발암성 및 면역독성을 나타내며, 식품, 곡류 및 정육 등에 잔류한다고 알려져 있다. 최근 우리나라의 된장, 간장등 발효식품에서도 OA가 검출되었다는 보고가 있어 OA에 대한 관심이 높아지고 있다. 본 연구에서는 OA의 전반적인 위해성 평가의 일환으로 OA의 독성 표적장기인 신장에 초점을 맞추어 신장독성 감소방법을 제시하고자 한다. 신장독성을 감소시키기 위한 대상물질로는 1) 기존에 독성감소 물질로 알려진 phenylalanine(Phe), 2) phenylalanine과 aspartic acid로 구성된 감미료인 아스파탐(Asp), 3) 녹차의 성분이며 free radical scavenger 및 antioxidant 작용이 있는 polyphenol(PP), 4) 최근 수명연장 효과가 있고 특히 신장질환에 대한 예방효과가 있다고 알려진 aloe 추출물(AE)을 선택하였다. 신장독성을 유발시키기 위하여 OA를 2.0 ㎎/㎏의 용량으로 2주간 연속 경구투여하였다. Phe(40 ㎎/㎏, i.p.)과 Asp(25 ㎎/㎏, p.o.)은 OA(2.0 ㎎/㎏, p.o.)와 병용투여하였으며, PP(200 ㎎/㎏, p.o.)는 OA 투여 2주전부터, AE(50 ㎎/㎏, i.v.)은 3일전부터 전처리하여 OA(2.0 ㎎/㎏, p.o.)와 2주간 병용투여하였다 신장독성의 확인은 혈청중 BUN, creatinine치 및 뇨중 γ-glutamyltranspeptidase와 N-acetyl-β-D-glucosarninidase의 활성을 측정하였고, 신장에 대한 조직병리 검사를 실시하였다. 실험결과, OA를 2주간 2.0 ㎎/㎏용량으로 투여한 결과 신장독성이 유발되었으며, 독성 감소물질로 사용한 4개의 화합물 모두 혈액 및 뇨중 신장독성 지표를 유의성있게 감소시켰다. 조직병리 검사결과 OA에 의하여 신장의 근위세뇨관에 변성이 유발되었으며, 4개의 화합물 처리군에서는 변성이 관찰되지 않았다. 이러한 결과로부터 Phe, Asp, PP및 An는 모두 OA에 의한 신장독성을 감소시킬 수 있으며, OA에 의한 신장독성 유발에는 Phe에 대한 경쟁작용 및 free radical생성이 관여되어 있음을 확인할 수 있었다

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol β-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with 20 μM cisplatin and 80 μM dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with 80 μM dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 ㎎/㎏, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 ㎎/㎏, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

Background : In this study, we investigated the renoprotective effects of serotonin and its derivatives, on the renal function and expression of inflammation and apoptosis in cisplatin-induced nephrotoxicity mice. Methods and Results : Serotonin and its derivatives were orally administered at a dose of 7.5 mg/kg body weight for 5 days before the intraperitoneal injection of cisplatin 20 mg/kg body weight, and the effects were compared with those of vehicle-treated nephrotoxicity control and normal groups. In the serum and kidney, renal function parameters, reactive oxygen species and expression of protein related to pro-oxidant, antioxidant, inflammation and apoptosis were examined. As a result, serotonin and its derivatives administrations to nephrotoxicity mice lowered serum BUN and creatinine concentrations. These results were derived, at least in part, from attenuation the expression of antioxidant enzymes-related proteins, SOD and GPx. In the cisplatin-induced renal condition, augmented p-p38, p-ERK and p-JNK (mitogen-activated protein kinase pathway) were reduced with a increase in antioxidant enzymes on serotonin and its derivatives treatment. Moreover, in the serotonin and its derivatives-treated groups, NF- κB-induced inflammatory factors and apoptotic protein expressions were regulated in the kidney. Conclusion : The present study indicates that serotonin and its derivatives exerts a renoprotective effect against cisplatin-induced nephrotoxicity through the recovery of kidney function deterioration and attenuation of renal inflammation and apoptosis by regulating oxidative stress condition.

Mercuric chloride, inorganic compound, is one of the most important drugs that has been used in the field of argriculture, antisyphilitica and anticeptics, but it is not used clinically at present. We have studied the effect of testosterone on the mercuric chlorideinduced nephrotoxicity. Renal lipid peroxide concentration of male rat treated with mercuric chloride was significantly increased in comparison with that of the female rat, it showed similar effects on testosterone pretreatment. Changes in renal catalase and glutathione peroxidase activities were not siginificantly different in testosterone-treated groups. But, renal xanthine oxidase and aldehyde oxidase activities of testrosterone-treated group given mercuric chloride significantly increased in comparison with that of the testosterone-treated alone. Animals treated with testosterone prior to mercuric chloride showed more severe damage on histological observations than those treated with testosterone only. Consequently, we suggest that the mercuric chloride-induced nephrotoxicity might be renal lipid peroxide generating enzyme system by testosterone.