Pharmacodynamics and pharmacokinetics of a novel phenolic hepatoprotective agent following single and multiple oral administration to healthy and liver-injured rats
May 2026· Free radical research· Vol 60, pp. 529 - 541· 0 citations· 42 references
Medicine
TL;DR
IBP demonstrated significant hepatoprotective effects in CCl4-induced liver injury, mitigating lipid peroxidation, inflammation, and necrosis, and demonstrated significant hepatoprotective effects following repeated dosing.
Abstract
Abstract Antioxidants play a crucial role in the treatment of liver pathologies, given that oxidative stress is involved in the pathogenesis of many hepatic diseases. This study aimed to investigate the pharmacodynamic and pharmacokinetic properties of the antioxidant 2,6-diisobornyl-4-methylphenol (IBP) in a rat model of carbon tetrachloride (CCl4)-induced liver injury. The introduction of IBP resulted in a 1.4- to 2-fold decrease in serum hepatic enzyme levels, a 25% and 18% rise in glutathione peroxidase and superoxide dismutase concentrations, respectively, and a 14% reduction in hepatic catalase activity compared with the negative control. Treated animals exhibited a 45% reduction in malondialdehyde (a marker of oxidative stress) and an 18% decrease in interleukin-6 levels relative to controls. The compound mitigated CCl4-induced liver damage and promoted restoration of liver function. Liver pathology affected the plasma exposure of IBP after a single administration, but pharmacokinetics normalized following repeated dosing. Bioavailability was 60% after a single dose and increased to 119% after multiple administrations. IBP demonstrated significant hepatoprotective effects in CCl4-induced liver injury, mitigating lipid peroxidation, inflammation, and necrosis. The initial reduction in systemic exposure following a single dose in pathological conditions may be attributed to impaired absorption and elevated metabolic consumption due to oxidative stress.
Background: Naturally derived compounds with antioxidant and hepatoprotective potential are being actively explored. 2′,6′-Dihydroxyacetophenone (DHDA), a phenolic compound, has shown antioxidant properties, but its role in diabetic liver injury remains inadequately investigated. Aim and objectives: This study aimed to assess the protective effects of DHDA on diabetes-induced liver injury in a rat model. Materials and methods: Acute toxicity was conducted by using mice. Diabetes was induced in Wistar rats using streptozotocin (STZ) following nicotinamide(NA) pretreatment. Animals were divided into four groups: normal control, diabetic control, DHDA at dose of 30 mg/kg, and DHDA at dose 60 mg/kg. DHDA was administered orally for three weeks. Fasting blood glucose (FBG), body weight, food intake and, water intake were evaluated. In addition, the biochemical parameters, in-Vitro antioxidant and the histopathology of liver were analyzed. Result: 300 mg/kg is the safe dose of DHDA. DHDA significantly reduced FBG and glycated haemoglobin (HbA1c) levels in diabetic rats. Elevated liver enzymes and oxidative stress markers were markedly attenuated, while endogenous antioxidant defences were restored, particularly at dose of 60 mg/kg. In vitro assays confirmed dose-dependent free radical scavenging activity. Histopathological examination showed notable improvement in hepatic architecture. Conclusion: DHDA exhibits significant antihyperglycaemic, antioxidant, and hepatoprotective effects in diabetic rats, highlighting its potential as a therapeutic candidate for diabetes-associated liver injury.
Rosmarinus officinalis extract may exert protective effects against MTX-induced hepatorenal injury through antioxidant and anti-inflammatory mechanisms, however, further studies are required to confirm these effects and validate their therapeutic potential.
Lana Muhammed, Nadia Salih· Open Veterinary Journal· 0 citations
ABSTRACT Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis. Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria. Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups. Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.
S. Ahmedova, M. Asrarov, S. Mirzakulov et al.· Drug Target Insights· 0 citations
Chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels, contributing to a reduction in AST and LDH activity.
T. G. Yakupova, A. Gizatullina, D. Karimov et al.· Experimental and Clinical Ga...· 0 citations
Pretreatment with PEIV significantly mitigated effects of LPS-induced liver injury by regulating biochemical parameters, reducing oxidative stress and inflammation, and preserving liver architecture, suggesting its potential as a natural therapeutic agent for liver diseases.
S. Anadozie, A³ Maryam, Theophilus I. Ebe et al.· Comparative Clinical Patholo...· 0 citations
Overall, chrysin demonstrates potent protective potential against PFOA-induced liver injury and may serve as a promising therapeutic candidate for environmental toxin-associated hepatotoxicity.
A. B. Awolesi, Moses C. Antiya, S. A. Praise· Innovative Medicines & O...· 0 citations
