Treatment and protective effects of metalloproteinase inhibitors alone and in combination with N-Acetyl cysteine plus vitamin E in rats exposed to aflatoxin B1

Abstract

This study was conducted to investigate the effects of matrix metalloproteinase (MMP) inhibitors dexamethasone and minocycline administrations -both single and in combination with N-acetylcysteine (NAC) and vitamin E-on the tissue distribution and lethal dose (LD)₅₀ of aflatoxin (AF)B₁ in rats. We performed this study on male Wistar rats (8-10 weeks) in two phases. In the first phase, rats were administered dexamethasone (5 and 20 mg/kg) and minocycline (45 and 90 mg/kg), both as single treatments and in combination with NAC (200 mg/kg) and vitamin E (600 mg/kg); these treatments followed AFB₁ administration (2 mg/kg). In the second phase, the therapeutic effect value (TEV) was calculated to determine the treatment effect on the LD₅₀ level of AFB₁. The tissue affinity of AFB1 from high to low was liver, kidney, intestine, brain, heart, spleen, lung, testis, and vitreous humor, respectively. Dexamethasone at the 20 mg/kg dose significantly reduced AFB₁ concentrations in the plasma and the other tissues, except for the vitreous humor. The effects of minocycline on the plasma and tissue concentrations of AFB₁ varied by dose and tissue. The combinations of dexamethasone or minocycline with NAC and vitamin E increased the AFB₁ concentrations in the plasma and all tissues, except for vitreous humor and liver. In male rats, the LD₅₀ value of AFB₁ was 11.86 mg/kg. The TEV of dexamethasone (20 mg/kg) was calculated to be 1.5. Dexamethasone can be administered in repeated doses at ≥20 mg/kg to increase survival in AFB₁ poisoning.

Keywords: Aflatoxin B(1); Dexamethasone; Minocycline; Rat; Tissue concentration.