Glycyrrhizic acid ameliorates sodium nitrite-induced lung and salivary gland toxicity: Impact on oxidative stress, inflammation and fibrosis

Hum Exp Toxicol. 2021 Apr;40(4):707-721. doi: 10.1177/0960327120964555. Epub 2020 Oct 8.

Abstract

Despite wide application of sodium nitrite (SN) as food additive, it exhibits considerable side effects on various body organs at high dose or chronic exposure. The aim of this study was to test whether Glycyrrhizic acid (GA) could ameliorate SN-induced toxicity in lung and submandibular salivary gland (SMG). A sample size of 30 adult male albino rats was randomly allocated into 3 groups. Group 1 served as control group. Rats were treated orally with 80 mg/kg of SN in group 2 or SN preceded by (15 mg/kg) GA in group 3. Lung & SMG tissues were used for oxidative stress assessment, examination of histopathological changes, fibrosis (MTC, TGF-β and α-SMA) and inflammation (TNF-α, IL-1β and CD-68). Concurrent administration of GA ameliorated pulmonary and salivary SN-induced toxicity via restoring the antioxidant defense mechanisms with reduction of MDA levels. GA reduced the key regulators of fibrosis TGF-β and α-SMA and collagen deposition. In addition to reduction of inflammatory cytokine (TNF-α, IL-1β) and macrophages recruitments, GA amended both pulmonary and salivary morphological changes. The present study proposed GA as a promising natural herb with antioxidant, anti-inflammatory and antifibrotic effects against pulmonary and salivary SN-induced toxicity.

Keywords: Glycyrrhizic acid; fibrosis; lung; oxidative stress; sodium nitrite; submandibular gland.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Fibrosis
  • Glutathione / metabolism
  • Glycyrrhizic Acid / pharmacology
  • Glycyrrhizic Acid / therapeutic use*
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Salivary Glands / drug effects*
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Sodium Nitrite / toxicity*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Malondialdehyde
  • Glycyrrhizic Acid
  • Glutathione
  • Sodium Nitrite