Amorphous silica nanoparticles (nSP50) exacerbate hepatic damage through the activation of acquired cell-mediated immunity

Due to their innovative functions, the use of nanoparticles in various industries has been expanding. However, a key concern is whether nanoparticles induce unexpected biological effects. Although many studies have focused on innate immunity, information on whether nanoparticles induce biological responses through effects on acquired immunity is sparse. Here, to assess the effects of amorphous silica nanoparticles on acquired immunity, we analyzed changes in acute toxicities after pretreatment with amorphous silica nanoparticles (50 nm in diameter; nSP50). Pretreatment with nSP50 biochemically and pathologically exacerbated nSP50-induced hepatic damage in immunocompetent mice. However, pretreatment with nSP50 did not exacerbate hepatic damage in immunodeficient mice. Consistent with this, the depletion of CD8+ cells with an anti-CD8 antibody in animals pretreated with nSP50 resulted in lower plasma levels of hepatic injury markers such as ALT and AST after an intravenous administration than treatment with an isotype-matched control antibody. Finally, stimulation of splenocytes promoted the release of IFN-γ in nSP50-pretreated mice regardless of the stimulator used. Moreover, the blockade of IFN-γ decreased plasma levels of ALT and AST levels in nSP50-pretreated mice. Collectively, these data show that nSP50-induced acquired immunity leads to exacerbation of hepatic damage through the activation of cytotoxic T lymphocytes.

Corchorus olitorius L. Leaf Extract Protects Rats from Acrylamide-Induced Hepatic Injury

Acrylamide is a water-soluble compound that forms during the high-temperature cooking of starchy foods and has carcinogenic, neurotoxic, and genotoxic properties. Also, short-term exposure to acrylamide has been shown to cause significant hepatic injury in laboratory animals, along with disruption of antioxidant defense mechanisms due to excessive ROS production. Therefore, dietary antioxidants are believed to be useful in combating the negative effects of acrylamide. Corchorus olitoris L., also known as molokhia in Arabic, is a leafy vegetable which is shown to possess potent antioxidant and organoprotective properties. In this study, rats were administered with an aqueous extract of molokhia leaves to see if it could protect them against acrylamide-induced hepatic damage. Hepatic injury markers included serum total protein, total bilirubin, ALT, AST, and ALP, while oxidative stress markers included MDA, GSH, CAT, and SOD after dosing with three levels of extract (100, 250, and 500 mg/kg) for 21 days. Results indicated that the extracts substantially reduced elevated levels of bilirubin, ALT, AST, ALP, and MDA to normal levels at all doses. The extracts also brought serum protein, GSH, CAT, and SOD levels back to normal. Although the restoration of serum hepatic enzyme levels was dose dependent, no specific dose dependent relationship was found for serum proteins, MDA, GSH, CAT, or SOD activities. The study's findings show that molokhia leaves extract protects against acrylamide-induced hepatic damage by virtue of its good radical scavenging and anti-lipiperoxidative properties conferred by phenolics, flavonoids, and alkaloids.

A CASE REPORT REGARDING MANAGEMENT OF KAMALA THROUGH AYURVEDA

Ayurveda is traditionally skilful in treating liver diseases for centuries. Although named Jaundice as a liver disorder was not mentioned in Ayurveda literature but based on common characteristics and Pathology, Kamala can be correlated with jaundice. Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepa- tocellular dysfunction, or biliary obstruction. Jaundice occurs in settings of cholestasis or inability to effectively secrete bile as well as disorders of bilirubin metabolism and hepatocellular dysfunction. Today's lifestyle with un- hygienic and poor dietary habits and alcoholic habits, etc are responsible factors to promote hepatic damage which is clinically reflected as Kamala. This paper discusses a patient seen in the OPD of Kayachikitsa Quadra Institute of Ayurveda Roorkee Haridwar. Her chief complaints Udara shool (pain in the abdomen), Kshudha Mandhya (loss of appetite), Daurbalya (weakness), Hrullas (Nausea), Mutrapitata (yellow discolouration of urine, Vibhandha (constipation) for 15 days. This patient was effectively treated by the combination of Kutaki Churna, Triphala, Trivrita Churna, Bhunimba Churna, Arogya Vardhini Vati, Phalatrikadi Kashaya, Punarnava Mandoor and Liv 52. All the symptoms showed highly significant results. Hence it can be concluded that these medicines are very effective in patients with jaundice. Keywords: Udara shool, Kshudha mandhya, Daurbalya, Hrullas, Mutrapitata, Vibhandha.

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.

Traditional Chinese Medicine Yang-Gan-Wan Alleviated Experimental Hepatic Damage by Inhibiting Oxidation, Inflammation, and Apoptosis in Cell and Mouse Models

A hepatoprotective medicine, Yang-Gan-Wan (YGW), was used to treat hepatic damage in cell and mouse models. We performed a 1,1-diphenyl-2- picrylhydrazyl (DPPH) assay and found that YGW exhibited a significantly high free radical scavenging ability. Furthermore, the results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that YGW treatment could alleviate lipopolysaccharide (LPS)-induced damage in Kupffer cells (liver macrophages). Enzyme-linked immunosorbent assay results demonstrated that YGW treatment could alleviate LPS-induced inflammation in Kupffer cells by inhibiting the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. By quantifying the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), we found that YGW treatment could alleviate hepatic damage and improve immunity in acetaminophen- (APAP-) treated mice by inhibiting the expression of ALT and AST. The findings of hematoxylin and eosin and Masson’s trichrome staining indicated that YGW treatment could alleviate hepatic damage and reduce collagen fiber formation in the liver tissue of APAP-treated mice. Furthermore, immunohistochemistry staining and Western blot results showed that YGW treatment could alleviate oxidative stress, inflammation, and apoptosis in the liver tissue of APAP-treated mice by enhancing superoxide dismutase 2 (SOD2) expression but inhibiting TNF-α and caspase 3 expression. Our results suggest that YGW treatment exerted hepatoprotective effects on LPS-treated Kupffer cells and APAP-treated mice by inhibiting oxidation, inflammation, and apoptosis.