Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice

Abstract

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl₂) in mice. Methods: In vitro phytochemical screening and the metal-chelating activity of UPLE were ascertained. Four groups of forty male mice were used (n = 10) as follows; Group 1 (G1) was a negative control. G2 was injected i.p., with UPLE (100 mg/kg b. wt) daily. G3 was injected i.p., with Cd (5 mg/kg b. wt) daily. G4 was injected with Cd as in G3 and with UPLE as in G2. On day 11, the body weight changes were evaluated, blood, and serum samples were collected for hematological and biochemical assessments. Liver tissues were used for biochemical, molecular, and histopathological investigations. Results: The results showed that UPLE contains promising secondary metabolites that considerably lessen the negative effects of Cd on liver. Furthermore, UPLE inhibited oxidative stress and inflammation; restored antioxidant molecules; and promoted nuclear-related factor-2 (Nrf-2) expression. Also, UPLE improved the histopathological alterations induced by Cd. Discussion: This study explored the beneficial role of UPLE treatment in Cd-induced liver injury through enhancing Nrf-2 signaling and antioxidant enzyme gene expression in the liver of mice. Therefore, UPLE could have valuable implications against hepatotoxicity induced by environmental cadmium exposure. Which can be used as a chelating agent against Cd.

Keywords: Urtica pilulifera; antioxidants; cadmium; hepatotoxicity; nuclear-related factor-2.

FIGURE 1

GC-MS profile chromatogram of Urtica pilulifera leaves extract.

FIGURE 2

The phytochemical components that are most prevalent in Urtica pilulifera leaves extract.

FIGURE 3

Effect of UPLE on the percentages of body weight changes of cadmium-intoxicated mice. I. B. wt.: Initial body weight; F. B. wt.: Final body weight; UPLE: Urtica pilulifera leaves extract; Cd: Cadmium. The values represented as means ± S.D (n = 10). Means that do not share a letter in each column are significantly different (p ≤ 0.05).

FIGURE 4

Effect of UPLE on cadmium concentration in liver tissues of cadmium-intoxicated mice. UPLE: Urtica pilulifera leaves extract; Cd: Cadmium. The values represented as means ± S.D (n = 10). Means that do not share a letter in each column are significantly different (p ≤ 0.05).

FIGURE 5

Effect of UPLE on hepatic inflammatory biomarkers and nuclear factor erythroid 2-related factor 2 of cadmium-intoxicated mice. (A) Interleukin-1β (IL-1β), (B) Tumor necrosis factor-α (TNF-α), and (C) Nuclear factor erythroid 2-related factor 2 (Nrf-2). UPLE: Urtica pilulifera leaves extract; Cd: Cadmium The values represent means ± S.D. (n = 10). Means that do not share a letter were significantly different (p < 0.05).

FIGURE 6

(A) The liver section photomicrograph of the normal control group demonstrates the typical hepatic architectures, including regular central veins (CV), normal hepatocytes (H), normal blood sinusoids (Bs), and Kupffer cells (K) (B) The majority of the hepatocytes in the UPLE control group’s liver are normal, with normal Bs and Ks (C) The Cd-injected group’s liver section shows abnormal blood sinusoids with distinct K, cellular infiltrations (*), vacuolated and degraded cytoplasm (V), and disorganized hepatic architecture (D) The liver section of the Cd/UPLE treated group exhibits improved hepatic organization with reduced cellular infiltrations and congestion. (X 400). (E) Histopathological scoring displaying infiltration of inflammatory cells and hepatic damages in Cd-intoxicated group. The values represent means ± S.D. (n = 10). Means that do not share a letter were significantly different (p < 0.05).