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The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression. [ABSTRACT FROM AUTHOR] more...

Fruits of Ammi majus, commonly called bishop's weed, contain a significant amount of furanocoumarins. Alloimperatorin (Allo, 6) was isolated from the free coumarin fraction of fruits, beside 8-hydroxypsoralen (1), methoxsalen (2), heraclin (3), isoimperatorin (4), imperatorin (5), isoheraclenin (7) and heraclenin hydrate (8). Piroxicam (Px) is a widely used pain-relieving drug that demonstrated side effects, including gastric ulceration and hepatorenal toxicity. This study aimed to investigate the protective potential of Alloimperatorin against Px-induced gastric ulceration and hepatorenal toxicity. Rats were divided into four groups: Negative control, Px-induced rats, Allo + Px co-treated group, and Pc + Px co-treated group. Allo (25 mg/kg body weight) and Pc (25 mg/kg body weight) treatments were received 5 days before and 4 days after Px intoxication for 4 days (50 mg/kg body weight). Serum prostaglandin E2 (PG-E2) and liver and kidney functions were measured. Oxidative stress markers were evaluated in the three tissues. Histopathological features and caspase-3 immunoexpression were monitored Px triggered gastric ulceration, increased indices of liver and kidney functions, decreased PG-E2 levels, provoked oxidative stress, and activated caspase-3 immunoexpression. Co-treatment with Allo demonstrated protective activities. Alloimperatorin exhibited anti-oxidative, anti-inflammatory, and anti-apoptotic activities. [ABSTRACT FROM AUTHOR] more...

Liver and kidney role in detoxification and drug metabolism increases the risk of their poisonous injury. Topiramate (TMP) is an effective popular migraine prophylaxis that is accepted for utilize in adults and teenagers. Therefore, the target of this research is to estimate the potential toxic effects of TMP on liver and kidney in male mice. Thirty-two adult albino male mice were divided into four groups (n = 8 mice). Group I of animals was given saline solution and used as negative control. The other three groups were administrated TPM at doses (100, 200 and 400 mg/kg) for 28 days. Genotoxicity was evaluated by comet assay and DNA fragmentation by Diphenyleamine. Biochemical investigation was achieved by estimating liver enzymes (AST, ALT), alkaline phosphatase (ALP) creatinine and uric acid. In addition, measurement of the antioxidant enzymes, malondialdehyde and nitric oxide were performed in both two tissues of liver and kidney. Microscopic examination of hematoxyline and eosin (H&E), tumor necrosis factor (TNF-α) and caspase3 stained sections were done to explore the effect of topiramate on mice tissues of liver and kidney. The data revealed that TPM showed dose dependent toxicity that represented in: DNA damage in tested cells and increased level of liver enzymes, creatinine and uric acid as markers of toxicity. Topiramate significantly diminished antioxidant enzymes activities and elevated the level of malondialdehyde and nitric oxide. In addition, TPM caused histopathological alterations and dose dependent positive immune reaction for TNF--α and caspase 3 in kidney and liver tissues. The results showed that Topiramate has marked toxicity in liver and kidney of mice. [ABSTRACT FROM AUTHOR] more...

This study aimed to screen different extracts (E) such as total ethanol (TE), petroleum ether (PE) chloroform (CH), ethyl acetate (EA) and methanol (AM) extracts of Peltophorum africanum Sond. (PA) and Saraca indica L. (SI) leaves (family fabaceae) for their in-vitro antidiabetic activity using α-amylase inhibition assay. The extracts that showed remarkable in vitro activity were further subjected to in vivo anti-diabetic assessment using streptozotocin-induced diabetes model in experimental animals where serum glucose, C-peptide, liver glycogen content in addition to lipid peroxide level in both serum and liver were estimated biochemically in normal and diseased rats. The average percent of weight change and kidney to body weight ratio percent were calculated for all animal groups. Histopathological examination of pancreas, liver and kidney sections isolated from all animals was carried out. UPLC/MS/MS analysis of TEE of PA and SI for chemical investigation was performed. Results of the in vitro anti diabetic activity revealed that EAE, PEE& TEE of PA and TEE & EAE of SI possessed the highest inhibitory activity as compared to acarbose. In vivo antidiabetic activity of the selected extracts revealed that animal groups treated daily with EAE of PA and SI exhibited a significant improvement in carbohydrate metabolism and lipid peroxide level, with superior effect in comparison with that of TEE and PEE of both plants. Histopathological findings showed marked protection particularly in sections isolated from animals treated with EAE of PA. UPLC/MS/MS analysis of TEE of both plants identified 46 metabolites belonging to various classes. It could be suggested that active extracts of both plants could be considered as potential natural antioxidant and anti-diabetic agents. [ABSTRACT FROM AUTHOR] more...

Protection against liver injury and its consequences is considered an essential issue to minimize the number of annual deaths caused by liver diseases. The present study was designed to evaluate the potential role of pomegranate extract (PE) and/or curcumin in the regression of thioacetamide (TAA)-induced liver fibrosis, focusing on their modulatory effects on Nrf2/HO-1, NF-κB, and TGF-β/Smad3 signaling pathways. Liver fibrosis was induced in male Wistar rats by intraperitoneal injection of TAA (100 mg/kg) three times a week, for 8 weeks. To assess the protective effects of PE and/or curcumin against TAA-induced liver fibrosis, rats were treated on a daily basis with oral doses of PE (200 mg/kg) and/or curcumin (200 mg/kg) for 8 weeks. The results indicated that PE and/or curcumin attenuated TAA-induced liver fibrogenesis, as evidenced by a significant improvement in the liver function tests (AST, ALT, ALP, and albumin), oxidative stress biomarkers (MDA, SOD, and GSH), and inflammatory biomarkers (NF-ĸB, TNF-α, IL-1β, iNOS, TGF-β, and MPO), compared to TAA group. Moreover, treatment with PE and/or curcumin exerted a significant upregulation of Nrf2/HO-1 gene expressions along with significant downregulation of NF-ĸB, TGF-β, and phospho-Smad3 protein expressions, as well as α-SMA and collagen-1 gene expressions. The histopathological examination has corroborated these findings. In conclusion, hepatoprotective activities of PE and/or curcumin could be linked to their abilities to modulate Nrf2/HO-1, NF-κB, and TGF-β/Smad3 signaling pathways. It is worth noting that the combination of PE and curcumin exerted superior hepatoprotective effects against TAA-induced liver fibrosis, as compared to monotherapy. [ABSTRACT FROM AUTHOR] more...

Context:Camel milk (CM) is recommended for liver disease patients in Egypt for a strong belief that it has a curative effect. Objective:The effect of consumption of CM with or without chemotherapeutic drug cisplatin was evaluated on induced hepatocarcinogenesis in rats. Materials and methods:Wistar male rats (56) were divided into eight groups (7 rats each). Group I was control. Hepatocarcinogenesis was initiated by a single dose of intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg BW) and promoted by phenobarbitone (500 ppm) in drinking water in groups V, VI, VII and VIII. Treatment started from 28th till 38th week using CM (5 mL/day) and/or cisplatin (5 mg/kg/3 weeks) in groups II, III IV, VI, VII and VIII. Biochemical analysis, lipid peroxidation and superoxide dismutase (SOD) activity in liver tissue were performed. Histopathology of liver and kidney and immunohistochemistry of placental glutathione-S-transferase (P-GST) in liver were performed and analyzed using image analysis. Results:Albumin concentration and SOD activity were 3.13 ± 0.23 and 311.45 ± 41.71 in group VII (DENA & cisplatin), whereas they were 4.3 ± 0.15 and 540.5 ± 29.94 in group VII (DENA, CM and cisplatin). The mean area of altered hepatocellular foci and P-GST altered foci decreased in group VI (DENA and CM) (1049.6 ± 174.78 and 829.1 ± 261) and group VIII (cisplatin and CM) (1615.12 ± 436 and 543.9 ± 127) compared to group V (DENA only) (4173.74 ± 510.7 and 3169.49 ± 538.61). Cisplatin caused chronic interstitial nephritis, which was slightly alleviated in group VIII (CM and cisplatin). Conclusions:CM had an antioxidant effect and together with cisplatin managed to decrease hepatocarcinogenesis. [ABSTRACT FROM PUBLISHER] more...

Context:Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties. Objective:Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO. Materials and methods:Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, andviaoral gavage given indomethacin (10 mg/kg) or CPO (400 mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened. Results:Amounts of α-, β-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177 mg/kg oil, respectively. In COO, α, β, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, β-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6 mg GAE/g, respectively. Acute toxicity test determined that 400 mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10 mg/kg) or CLO (400 mg/kg) induced a significant (p < 0.05) reduction by 31.3 and 27.4%, respectively, in rat paw oedema as compared with the carrageenan-treated group. Indomethacin induced a significant ulcerogenic effect with an ulcer index of 19. Oral treatment of CPO showed no ulcerogenic effect, wherein no histopathological changes were observed. Conclusions:CPO, particularly CLO, could minimize acute inflammation. [ABSTRACT FROM PUBLISHER] more...