Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses

Abstract

Purpose Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. Methods Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed. Results MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture. Conclusion HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.

Human Placental Extract Delays In Vitro Cellular Senescence through the Activation of NRF2-Mediated Antioxidant Pathway

“…Placental extracts have shown antioxidant properties in both in vitro and in vivo models [ 17 , 18 , 19 , 20 , 21 , 22 ]. Therefore, we investigated whether HPE enhances ROS scavenging in H 2 O 2 -treated NHDFs.…”

“…Notably, HPE has been shown to mitigate oxidative stress at different levels: HPE ingredients, such as uracil, tyrosine, phenylalanine, tryptophan, and collagen-derived peptides, impair Fenton’s reaction [ 17 , 18 ]. HPE decreases ROS levels in cultured cells [ 19 , 20 ] and ameliorates tissue abnormalities induced by oxidative stress [ 20 , 21 , 22 ]. However, whether HPE slows oxidative stress-induced cellular senescence remains largely unknown.…”

Experimental medicinal hepatitis. Hepatoprotective effects of the drug Laennec in models of toxic liver injury with paracetamol or alcohol

“…Ранее, были проведены исследования эффективности ГПЧ на других моделях поражения печени: неалкогольном стеатогепатите (НАСГ, в т. ч. в сочетании с перегрузкой железом) [10] и при поражении печени антифолатным препаратом метотрексат [11].…”

“…Крысы, получавшие метотрексат, показали значительно повышенные уровни АСТ, АЛТ, ЩФ, общего билирубина, общего холестерина и триглицеридов. Подкожное введение ГПЧ снижало повышенные уровни этих маркёров дисфункции печени, уменьшало уровни МДА (как и в настоящем исследовании), уровни провоспалительных цитокинов ФНО-α, ИЛ-6 и ИЛ-10 и тормозило снижение глутатиона (GSH) и улучшало гистологическую структуру печени [11].…”

“…В печени крыс, получавших метотрексат и ГПЧ, установлены минимальные морфологические изменения гистологических признаков во всех исследованных образцах. При этом гепатоциты выглядели нормально (полигональные, с четкими краями клеток и хорошо выраженной цитоплазмой и ядрами), что указывает на очевидную защитную роль ГПЧ против действия метотрексата [11].…”