Experimental Cirrhosis: Liver Morphology and Function

Abstract

The aim was to establish the morphofunctional changes of liver in the experimental cirrhosis. Materials and methods: The research was conducted on 24 white male Wistar rats. Experimental cirrhosis of the liver was simulated by oral administration of CCl4 2 g/kg 2 times weekly for three months. From the selected fragments of the liver, histological specimens were done according to the conventional method and examined by light microscopy. The activity of the enzymes of cytolysis and cholestasis (ALT, AST, alkaline phosphatase), the content of components of bile (cholesterol, bilirubin and bile acids) were determined in the serum. In the blood and liver were determined the content of the final products of metabolism of nitric oxide: NO2 - and NO3 -; in the blood – the content of ceruloplasmin, lactate, pyruvate, middle molecular-weight protein MWP1 and MWP2. In the liver – the activity of succinate dehydrogenase (SDG) and cytochrome oxidase (CHO), N-demethylase and p-hydroxylase microsomal activity. The state of the system of prooxidants-antioxidants was judged by the content in the liver of thiobarbituric acid reactive substance (TBARS), lipid hydroperoxide (LHP), concentration of sulfhydril group (GSH), catalase activities (CAT), superoxide dismutase (SOD). The content of endothelial (eNOS) and inducible (iNOS) NO synthases, the concentration of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were determined by the enzyme immunoassay. Results: Cirrhosis of the liver, which is morphologically confirmed by the presence of prominent sclerosis in the periportal zones and the formation of umbel, is accompanied by the development of cytolysis and cholestasis processes with an increase in the content of components of bile in the blood (cholesterol, bilirubin and bile acids). An increase in the content of lipoperoxidation products and disturbance of the state of the enzymatic and non-enzymatic units of the antioxidant system, decrease in the activity of mitochondrial (succinate dehydrogenase and cytochrome oxidase) enzymes have been established. The activity of the detoxification processes decreases, namely the inhibition of N-demethylase and p-hydroxylase activity of the liver microsomes, so the manifestations of endotoxicosis increase. This is accompanied with decreased content of endothelial and an increased content inducible NO synthase, a concentration of a stable metabolite of nitric oxide nitrite anion in the blood increase and a decrease in the liver. Сonclusions: Experimental CCl4 cirrhosis is characterized morphologically by sclerosis in the periportal zones and the formation of umbao. The metabolic and functional cirrhoticliver is characterized by cytolysis and cholestasis activation, inhibition of detoxication, prooxidant-antooxidant, including nitrooxidative, disbalance.

Hematological and biochemical investigations on the effect of curcumin and Thymoquinone in male mice exposed to Thioacetamide

“…The present data revealed that the exposure to TAA increased serum ALT, AST, ALP and TB levels. Liver AST, ALT, ALP and TB are frequently used as biomarkers of liver injury and diseases ( Bozdağ and Eraslan, 2020 , Datsko et al, 2020 , Koyuncuoğlu et al, 2020 , Li et al, 2020 , Sun et al, 2021 ). Additionally, previous experimental studies showed that these parameters were significantly increased in animals exposed to TAA ( El-Baz et al, 2019 , Dwivedi et al, 2020 , Gowifel et al, 2020 , Bogahawaththa et al, 2021 , El-Gendy et al, 2021 , Younis et al, 2021 ).…”

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

“…Different multi-center, double-blind, placebo-controlled trials, showed that the oral SAM treatment (800-1600 mg/day) induced a significant decrease of the clinical biochemical indices of cholestasis and an improvement of symptoms of fatigue and pruritus [152][153][154][155]. In another study, a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated the effect and safety of ursodeoxycholic acid (UDCA), SAM and UDCA-SAM combination therapies for intrahepatic cholestasis of pregnancy (ICP).…”

“…At present the mechanisms determining the response to the treatment with Pegylated IFNα/Ribavirin are not completely known. A possible mechanism could be the HCV-induced viral interference with IFNα and JAK-STAT signaling, determined by the hypomethylation of STAT1 that facilitates the contact of STAT1 with its inhibitor PIAS1 (protein inhibitor of activated STAT1) [153]. In addition, two SNPs near the gene IL28B on chromosome 19 were found to be strongly associated with non-viral response [154,155].…”

Ефективність L-Орнітину L-Аспартату В Попередженні Ендотоксикозу І Порушень Мітохондріального Дихання При Гострому Токсичному Гепатиті

“…24. № 1 статності [4], пов'язаний із підвищенням активності синтази оксиду азоту (NOS) з подальшим посиленням мікроперфузії печінки [5]. Однак залежний від оксиду азоту (NO) механізм дії LOLA при гострому токсичному ураженні печінки недостатньо вивчено.…”