A comprehensive survey of warfarin-induced hepatic toxicity using histopathological, biomarker, and molecular evaluation.

Warfarin finds human application as anticoagulant therapy. Warfarin usage can cause liver damage and hemorrhage. Besides functioning as anticoagulant and causing continuous bleeding of pests, the mechanism of toxicity of warfarin is unknown. In this study, Wild female and male rats were administrated orally with warfarin for 18 days at 9, 18, 27.5, and 55 mg/kg, respectively. Hepatoxicity was determined by assessing, LD50, leukocyte counts, immunochemistry, histopathology, serum proteins, Western blotting, especially of markers of liver injury, such as AST, ALT & ALP, and markers of antioxidant and oxidative stress markers. Warfarin treatment decreased Nrf2 levels while it increased caspase 3, CYP2C9, COLL1A1. It caused cellular damage and fibrosis of liver. The plasma levels of markers of liver injury, AST, ALT, ALP, bilirubin and transferrin were increased. The plasma levels of albumin, IgG and antitrypsin were decreased. Warfarin treatment decreased RBC and total lymphocyte count while increasing selectively neutrophils. Warfarin exposure caused increased oxidative stress; increased LPO and decreased GSH, SOD, CAT and NO production. Oral exposure of rats with Warfarin leads to increased oxidative stress resulting into liver damage via CYP2C9 mediated by Nrf2 depletion.

Nanocurcumin and curcumin prevent N, N'-methylenebisacrylamide-induced liver damage and promotion of hepatic cancer cell growth.

Acrylamide (AC) is an environmental contaminant with cancer-promoting and cytotoxic properties, while curcumin (Cur.) is a phytochemical with documented anticancer and cytoprotective efficacy. Nanoparticle formulations can increase the efficacy of phytochemicals, so we examined the anticancer and hepatoprotective efficacies of nanocurcumin (N.Cur). Curcumin and nanocurcumin reduced HepG2 and Huh-7 cancer cell viability and increased apoptosis in the presence and absence of AC, while AC alone promoted proliferation. Furthermore, the anticancer efficacy of nanocurcumin was greater than that of curcumin. In mice, AC greatly increased hepatic expression of CYP2E1, P53, cleaved caspase-3, and COL1A1 as well as serum alanine aminotransferase and aspartate aminotransferase activities. These effects were reversed by nanocurcumin and curcumin. Nanocurcumin also reduced the histopathology and fibrosis caused by AC, and reversed AC-induced glycogen depletion. Nanoparticle formulation can increase the anticancer and hepatoprotective efficiencies of curcumin.

Assessment of the Toxicity of Aluminum Oxide and Its Nanoparticles in the Bone Marrow and Liver of Male Mice: Ameliorative Efficacy of Curcumin Nanoparticles.

The potential influence of nanoparticles (NPs) on the liver and bone marrow has received attention. The aim of this work was to evaluate the effect of nanocurcumin on the oxidative stress, apoptosis, and toxicity induced by Al2O3 and its NPs. The experimental animals (n = 72 mice) were divided into the following groups: group I, as a control; groups II and III, as aluminum oxide and its NPs (6 mg/kg); group IV, as aluminum oxide + nanocurcumin (Al2O3 + N-Cur, 20 mg/kg); and group V, as aluminum oxide NPs + nanocurcumin (Al2O3-NP + N.Cur., 20 mg/kg). Al2O3 and its NP groups significantly increased p53, Nrf2 levels, and the white blood cell count. They also decreased the Hsp70 level, antitrypsin, immunoglobulin G, and the red blood cell count. In addition, they significantly decreased the total and differential bone marrow cell counts and the maturation index ratio (MIR). Nanocurcumin (N.Cur.) reverted the previous proteins, blood parameters, total bone marrow cell count, and the MIR as M/E, I/Mg, MMI, I/Me, and EMI to normal. Furthermore, N.Cur. prevented apoptosis and reduced the histopathological score and collagen fiber percentage caused by Al2O3 and its NPs in the liver. Nanotechnology was used to increase the therapeutic efficiency of curcumin against the harmful effects of oxidative stress associated with Al2O3 NPs.

Impact of Glyphosate-Roundup® in the Ileal Structure of Male and Female Rats: A Morphological and Immunohistochemical Study.

The current study was aimed to evaluate the effects of variable doses of the weedicide glyphosate on the ileal (the final section of the small intestine) structure of rats of both sexes, using histological, histochemical, and ultrastructural methods. Forty animals were classified into four groups of 10 animals per group (five males and five females). The first group acted as a control, and the remaining groups were treated with glyphosate-Roundup® 25, 50, and 100 mg/kg body weight daily for 15 days. The results indicated extinct histopathological changes manifested in the deformation of villi, foci of leukocytic infiltration in the core of villi, and hyperplasia of goblet cells. Histochemical examination (Alcian blue and Periodic acid-Schiff stain) revealed a strong positive reaction of goblet cells and an increase in their number in all treated groups. In addition, the immunohistochemical investigation revealed the immunoreactivity of matrix metalloproteinase-9 expression. Furthermore, electron microscopic alternations were represented by the deformation of nuclei, destruction of microvilli, and deposition of lipid droplets. Collectively, the present findings indicate that treatment with glyphosate results in extensive morphological alternations to the ileal structure of rats of both sexes and that female rats are more affected than male rats are.

Adipose-derived mesenchymal stem cells rescue rat hippocampal cells from aluminum oxide nanoparticle-induced apoptosis via regulation of P53, Aß, SOX2, OCT4, and CYP2E1.

Mesenchymal stem cells (MSCs) possess a preventive capacity against free radical toxicity in various tissues. The present study aimed to demonstrate the reformative and treatment roles of adipose-derived MSCs (AD-MSCs) against severe toxicity in the hippocampal cells of the brain caused by aluminum oxide nanoparticles (Al2O3-NPs). Rats were divided into five experimental groups: an untreated control group, a control group receiving NaCl, a group receiving Al2O3-NPs (6 mg/kg) for 20 days, a group that was allowed to recover (R) for 20 days following treatment with Al2O3-NPs, and a Al2O3-NPs + AD-MSCs group, where each rat was injected with 0.8 × 106 AD-MSCs via the caudal vein. Oral administration of Al2O3-NPs increased the protein levels of P53, cleaved caspase-3, CYP2E1, and beta-amyloid (Aß); contrarily, AD-MSCs transplantation downregulated the levels of these proteins. In addition, the AD-MSCs-treated hippocampal cells were protected from Al2O3-NPs-induced toxicity, as detected by the expression levels of Sox2 and Oct4 that are essential for the maintenance of self-renewal. It was also found that AD-MSCs injection significantly altered the levels of brain total peroxide and monoamine oxidase (MAO)-A and MAO-B activities. Histologically, our results indicated that AD-MSCs alleviated the severe damage in the hippocampal cells induced by Al2O3-NPs. Moreover, the role of AD-MSCs in reducing hippocampal cell death was reinforced by the regulation of P53, cleaved caspase-3, Aß, and CYP2E1 proteins, as well as by the regulation of SOX2 and OCT4 levels and MAO-A and MAO-B activities.

Soya milk alleviates toxicity caused by citric acid in male mice: Histopathological and hematological studies.

This study evaluated the toxicity of citric acid and the benefits of soya milk (SM) for preventing damage in mice. Thirty-five mice were divided into groups: control, mice administered citric acid (CA group) for 30 days, mice administered SM before the administration of citric acid for 30 days (SM + CA group), mice administered citric acid for 15 days and left for recovery (R group), and mice in recovery receiving SM for 15 days (R + SM). Mice in CA and R groups displayed downregulated p53, increased cleavage of caspase 3, and upregulation of Nrf2, CYP1A1, ALT, and AST activity in the liver. In contrast, SM + CA and R + SM treated mice were protected against CA toxicity and showed reversal of p53 downregulation, reduced cleavage of caspase 3, downregulation of Nrf2, and an increase in liver function enzymes. SM administration also restored blood cell and hemoglobin content and general histology of hepatocytes. PRACTICAL APPLICATIONS: CA causes liver damage, increases inflammation, decreases blood cell numbers, and induces apoptosis. Some natural products, such as SM, have been used to scavenge free radicals that can cause liver damage and hemolysis. This study focuses on the effectiveness of SM in ameliorating CA toxicity and may be helpful in the food industry for managing oxidative stress that may be induced by common dietary constituents. SM may help suppress liver damage and inflammation.