Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats with streptozotocin-induced diabetes

Abstract

Reactive oxygen species have been related to the pathogenesis of various diseases, including diabetes mellitus. Nicotinamide has been used for the prevention of the diabetogenic effects of streptozotocin (STZ) in animals. In the present study we assessed the effect of diets with deficient, normal or 17-fold supplemented nicotinamide concentrations on the rate of lipoperoxidation in animals with STZ-induced diabetes. Male Wistar rats were divided into three groups kept on one of the diets for six weeks: DD, diabetic rats on a nicotinamide-deficient diet; DN, diabetic rats on a normal nicotinamide diet; and DS, diabetic rats on a nicotinamide-supplemented diet. During the fourth week of the experiment all animals were fasted for 24 hours and injected into the tail vein with a single STZ dose (40 mg/kg weight). Eight animals from each of the six groups were then sacrificed 24 hours, 1 week and 2 weeks after STZ injection. Mean pancreatic thiobarbituric acid reactive substances (TBARS) (nmol/mg tissue) were significantly lower in the DS group (p < 0.05) compared to the DN and DD groups at 24 hours and during the first week. Hepatic TBARS concentrations (nmol/mg protein) did not differ between groups. Mean hepatic reduced glutathione (GSH) levels were significantly higher (46.76 +/- 12.33 nmol/mg protein) in the DS group compared to the DD (32.90 +/- 6.70) and DN (24.55 +/- 6.41) groups, but only after the 24-hour period. Hepatic vitamin E consumption (microgram/g tissue) was considerable in the groups not supplemented with nicotinamide, whereas vitamin E levels were unchanged in the supplemented group. In contrast, plasma vitamin E levels were decreased in the normal and supplemented groups after 1 and 2 weeks. A higher N-methylnicotinamide excretion (microgram/24 hours) occurred in the supplemented group. We conclude that, after induction of diabetes with STZ, nicotinamide supplementation protected from the damage caused by the toxic action of STZ, promoting lower lipid peroxidation.

Diabetes, oxidative stress, and antioxidants: A review

“…Preventing the formation of hydroxyl radicals would be an efficient means to reduce hydroxylinduced damage, and several compounds have been tested as antioxidants in diabetic animals with varying success. For example, the increase in TBARS associated with diabetes is prevented by treatment with nicotinamide [61], boldine [62], melatonin [45,49,63], aspirin [74], L-arginine or sodium nitroprusside [67], probucol [51], ␣-lipoic acid [71,77], aminoguanidine [69], captopril, enalapril [65], or nitecapone [66], if this treatment is given before or immediately after the diabetogen.…”

“…These normalization effects are seen in kidney [58,59,62,65,66,78], liver [58][59][60][61][62]64,74], heart [51][52][53]77], brain [49], intestine [58], lung [60], pancreas [45,61,62], Diabetogens alloxan (ALX) or streptozotocin (STZ), administered to mice or Wistar or Sprague-Dawley (SD) rats, produced increases (⇑) or decreases (⇓) from normal levels of TBARS as indicated in the top line for each study. Dose and route of diabetogen administration is indicated in the second line of column 2, and the asterisk in line 3 indicates diabetogen treatment continued for the specified number of days.…”

“…Table 2 summarizes recent studies of the effects of various antioxidants on glutathione concentrations. Glutathione concentration is found to be decreased in the liver [50,[54][55][56][57][58][59]61,64,75], kidney [59], pancreas [45], plasma [63,67], red blood cells [63], nerve [76], and precataractous lens [70] of chemically induced diabetic animals. However, there is also some contradictory evidence of increased glutathione concentration in diabetic rat kidney [78] and lens [85].…”

“…Levels of glutathione are reported to be normalized by vanadyl [50], dehydroepiandrosterone (DHEA) [59], oil of Eruca sativa seeds [64], nicotinamide [61], L-arginine or nitroprusside [67], melatonin [63], and melatonin plus desferrioxamine [45] when these antioxidants are given prior to or at the same time as the diabetogen. However, antioxidants that fail to reverse the effects of established diabetes on glutathione levels include coenzyme Q 10 [54], quercetin [75], piperine [57], isoeugenol [55], PNU-104067F or PNU-74389G [56], DHEA [59], melatonin [58], and taurine [70].…”

Nicotinamide Reverses Neurological and Neurovascular Deficits in Streptozotocin Diabetic Rats

“…It has been shown to improve energy status in ischemic tissues (Yang et al, 2002), exhibit antioxidant properties (Melo et al, 2000;Shen et al, 2004), regulate neuronal calcium fluxes (Shen et al, 2004), and inhibit apoptosis (Maiese and Chong, 2003;Shen et al, 2004), making it an attractive potential agent for the treatment of DPN. Moreover, nicotinamide has been used in human clinical trials with a low incidence of side effects or toxicity (Gale et al, 2004).…”