Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.

Moringa oleifera leaf ethanol extract ameliorates lead-induced hepato-nephrotoxicity in rabbits

Objective: To evaluate the effect of Moringa oleifera leaf ethanol extract as an adjunct treatment on lead acetate induced hepato-nephrotoxicity in rabbits. Methods: Thirty-six male New Zealand White rabbits were assigned into two main groups. The first group (14 rabbits) served as normal control. The secondgroup (22 rabbits) was administered orally with lead acetate at a dose of 40 mg/kg/day, 5 days/week for 8 weeks. At the 4th and the 8th week of treatment, 6 animals (3 animals at each period) of the second group were sacrificed while the remaining animals (16 rabbits) were assigned randomly into 2 subgroups (8 rabbits each): treated and non-treated. The first subgroup was orally given 1 mL phosphate-buffered saline for further 4 weeks while the second subgroup was administered orally with Moringa oleifera leaf ethanol extract at a dose of 400 mg/kg/day for the same period. Blood samples were collected to determine hematological and serum biochemical indices. Tissue specimens were collected from the liver and kidney for evaluation of the oxidant/antioxidant markers and for histopathological examinations. Results: Lead acetate exposure decreased the mean body weight gain, hematocrit, hemoglobin, mean corpuscular volume, and lymphocytes count. Moreover, it markedly increased counts of monocytes and platelets, serum enzyme activity, levels of creatinine, total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Malondialdehyde level was markedly increased while the reduced glutathione content was significantly decreased in liver tissue of lead intoxicated-rabbits. Histopathological alterations were also noticed in the liver and kidney of lead intoxicated rabbits. Moringa oleifera leaf ethanol extract significantly improved hematological and serum biochemical parameters and histopathological structure of the liver and kidney. Conclusions: Moringa oleifera leaf ethanol extract ameliorates hemato-biochemical and histopathological alterations caused by lead acetate and improveshepatic and renal functions.