Increase in Kidney 8-Hydroxydeoxyguanosine Level with the Progression of Renal Failure

Dear Sir, It has recently become apparent that active oxygen produces damage to biological membranes, protein and DNA, playing a role in aging, carcinogenesis and the onset and pathological features of rheumatism and other diseases [1, 2]. Although fragmentation of the DNA chain and alteration of thymine glycol and thymidine glycol by active oxygen were reported previously by Okamoto [3], Yamamoto et al. [4] and Cathcart et al. [5], little is known about damage to purine bodies. However, Kasai and Nishimura [6, 7] recently demonstrated that deoxyguanosine (dG) in the DNA molecule is oxidized by oxygen radical to 8-hydroxydeoxyguanosine (8-OH-dG), and concluded that 8-OH-dG can be used as a new indicator of injury to DNA bases by oxygen radical. On the other hand, in some studies carried out by Paller et al. [8], Shah and Walker [9], Diamond et al. [10] and Rehan et al. [11], renal failure induced by renal ischemia or administration of glycerol, puromycin aminonucleoside or antiglomeru-lar basement membrane was ameliorated by treatment with scavengers of hydroxyl radical, superoxide anion and hydrogen peroxide. On the basis of these findings, they suggested the involvement of active oxygen in the onset of renal failure. Fillit et al. [12], Giardini et al. [13], Kuroda et al. [14] and Flament et al. [15] have also reported findings suggestive of histological damage by active oxygen in patients with renal failure, suggesting the possibility that patients with renal failure are generally under oxidative stress. However, the extent to which active oxygen contributes to the progression of renal failure at the organ level remains unclear. In order to investigate this issue, we studied the amount of 8-OH-dG in rat renal DNA. Male Wistar rats (body weight approx. 200 g) were used. Animals with renal failure were prepared by feeding them on an 18% casein diet containing 0.75% adenine (dosage of adenine approx. 350-360 mg/kg body weight) for 10,20 or 30 days. Normal animals were fed on an 18% casein diet for 10 days. In rats given adenine, it had been confirmed previously both histologically and biochemically that renal failure progressed as the period of adenine feeding was prolonged [16-23]. The level of serum constituents in experimental rats were as follows: in rats fed on the adenine diet, urea nitrogen levels were 3.2 times (50.5 ± 1.5 mg/dl) those in normal rats on the 10th experimental day, and 8.6 times higher on the 30th experimental day. An