Garlic and allopurinol attenuate hepatic apoptosis induced by fipronil in male albino rats

Regul Toxicol Pharmacol. 2019 Oct:107:104400. doi: 10.1016/j.yrtph.2019.05.025. Epub 2019 May 29.

Abstract

Fipronil (FPN) can induce oxidative tissue damage and may be contemplated as an apoptosis inducer. Our aim is to investigate the possible hepatoprotective roles of garlic or allopurinol (ALP) against fipronil subacute toxicity. Thirty-six mature male albino rats were randomly divided into six groups; the first group was saved as control (C), the 2nd (G) was orally intubated with 500 mg/kg aqueous garlic extract, and the 3rd (A) received 150 mg/L allopurinol in their drinking water. The 4th group (F) was administered 13.277 mg/kg fipronil by gavage, while the 5th (G + F) and 6th (A + F) groups received the same doses of garlic and allopurinol, respectively two hours before fipronil intoxication. Our results revealed that FPN significantly increased the hepatic malondialdehyde, protein carbonyl levels, and the enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase, but it decreased glutathione-S-transferase compared to the control group. Moreover, FPN exhibited significant up-regulation in the hepatic pro-apoptotic (Bax) and caspase-3 genes expression, down-regulation in the anti-apoptotic (Bcl-2) mRNA gene expression and induced DNA fragmentation. Surprisingly, garlic or allopurinol co-treatment ameliorated the hepatic lipid peroxidation, antioxidants disruption, and apoptosis induced by FPN. In conclusion, garlic and allopurinol relieved the oxidative injury and reduced the fipronil-induced apoptosis probably by improving the tissue antioxidant defense system.

Keywords: Allopurinol; Apoptosis; Fipronil; Garlic; Liver; Oxidative stress.

MeSH terms

  • Allopurinol / pharmacology
  • Allopurinol / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Garlic*
  • Glutathione / metabolism
  • Insecticides / toxicity*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Oxidoreductases / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Roots
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Pyrazoles / toxicity*
  • Rats

Substances

  • Bcl2 protein, rat
  • Insecticides
  • Plant Extracts
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Malondialdehyde
  • Allopurinol
  • Oxidoreductases
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • fipronil