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Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats

Abstract

Introduction and aim

Hydrogen sulfide (H2S) is an endogenously produced gas-structure mediator. It is proposed to have antioxidant, anti-inflammatory and antiapoptotic effects. Acetaminophen (N-acetyl-P-aminophenol; APAP) is an antipyretic and analgesic medication known as paracetamol. When taken at therapeutic doses there are few side-effects, but at high doses APAP can cause clear liver and kidney damage in humans and experimental animals. In this study, the effects of the H2S donor of sodium hydrosulfide (NaHS) on acute renal toxicity induced by APAP in rats were researched in comparison with N-acetyl cysteine (NAC).

Method

Rats were divided into six groups (n = 7) as control. APAP, APAP + NAC, APAP + NaHS 25 µmol/kg, NaHS 50 µmol/kg and NaHS 100 µmol/kg. After oral dose of 2 g/kg APAP, NAC and NaHS were administered via the i.p. route for 7 days. In renal homogenates, KIM-1 (Kidney Injury Molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), TNF-α and TGFβ levels were measured with the ELISA method for tissue injury and inflammation. In renal tissue, oxidative stress levels were identified by spectrophotometric measurement of TAS and TOS. Histopathologic investigation of renal tissue used caspase 3 staining for apoptotic changes, Masson trichrome and H&E staining for variations occurring in glomerular and tubular systems.

Results

NaHS lowered KIM-1, NGAL, TNF-α, TGF-β and TOS levels elevated in renal tissue linked to APAP and increased TAS values. NaHS prevented apoptosis in the kidney and was identified to ensure histologic amelioration in glomerular and tubular structures. NaHS at 50 µmol/kg dose was more effective, with the effect reduced with 100 µmol/kg dose.

Conclusion

H2S shows protective effect against acute renal injury linked to APAP. This protective effect reduces with high doses of H2S. The anti-inflammatory and antioxidant activity of H2S may play a role in the renoprotective effect.

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Correspondence to Fikriye Yasemin Ozatik.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Dumlupinar University, Animal Experiments Local Ethics Committee at which the studies were conducted (Decision no: 2017.07.01).

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This Study was carried out in Dumlupinar University, Experimental Animal Laboratory.

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Ozatik, F.Y., Teksen, Y., Kadioglu, E. et al. Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats. Int Urol Nephrol 51, 745–754 (2019). https://doi.org/10.1007/s11255-018-2053-0

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  • DOI: https://doi.org/10.1007/s11255-018-2053-0

Keywords

  • Acetaminophen
  • Rats
  • Acute renal injury
  • H2S
  • NaHS