Rat Hepatic Tissue Research Articles

Heavy metals altered the xenobiotic metabolism of rats by targeting the GST enzyme: An in vitro and in silico study

Among all the heavy metals, Pb, Cd, and As are the most harmful pollutants in the environment. They reach into the organisms via various levels of food chains i.e. air and water. Glutathione-s-transferase (GST, E.C. 2.5.1.18), a key enzyme of xenobiotics metabolism, plays an important role in the removal of several toxicants. The present study aimed to evaluate any inhibitory action of these heavy metals on the GST enzyme isolated from the hepatic tissues of rats. A 10 % (w/v) homogenate of rat liver was prepared in cold and centrifuged at 4 °C at 9000xg for 30 min. The supernatant was collected and kept frozen at −20 °C or used fresh for carrying out different experiments. The activity of GST was monitored spectrophotometrically at 340 nm using 220 μg of soluble protein with varying equal substrate concentrations (0.125–2 mM) in phosphate buffer (50 mM, pH 6.5). To assess the impact of heavy metals on the enzyme activity, different concentrations of Cd (0–0.6 mM) and Pb (0–2 mM) were added to the reaction mixture followed by monitoring the residual activity. The optimum temperature and pH of rat liver GST were found to be 37 °C and 6.5, respectively. The Km value for GST was 0.69 mM and the Vmax was found to be 78.67 U/mg. The Cd and Pb significantly altered the kinetic behaviour of the enzyme. The Vmax and Kcat/Km parameters of GST were recorded to be decreased after interaction with Cd and Pb individually and showed a mixed type of inhibition pattern suggesting that these inhibitors may have a greater binding affinity either for the free enzyme or the substrate-enzyme complex. These metals showed a time-dependent enzyme inhibition profile. Cd was found to be the most potent inhibitor when compared to other treated metals; the order of inhibitory effect of metal ions was Cd>Pb>As. The in silico ion docking analysis for determining the probable interactions of Cd and Pb with fragmented GST validated that Cd exhibited higher inhibition potential for the enzyme as compared to Pb. The results of the present study indicated that exposure of both the Cd and Pb may cause significant inhibition of hepatic GST; the former with higher inhibitory potential than the later. However, As proved to be least effective against the enzyme under the aforesaid experimental conditions.

Melatonin protects against chromium induced oxidative stress-mediated changes in energy metabolism of rat hepatic, cardiac and renal tissues

Chromium (Cr) is one of the most prevalent and potentially hazardous heavy metal found in the environment that can cause carcinogenic, genotoxic, and organ-specific irreversible complications. The most severe adverse outcome of Cr on humans involves oxidative stress. Melatonin was evidenced to alleviate such stress with various mechanisms including antioxidative potential and metal chelation. Male Wistar rats were divided into 4 groups and treated for 14 days. The first group (control) was treated with vehicle; the second group was orally administered with melatonin (20 mg/kg b.w./day); the third group was injected with sodium dichromate dihydrate (5 mg/kg bw, s.c. every alternate day); and the fourth group was administered with melatonin, 30 min before Cr administration. The treatment of rats with Cr (VI) was found to affect the metabolic pathways by altering the activities of enzymes possibly through uncompetitively binding with them. The current study also demonstrated that melatonin efficiently preserved the glucose levels and blood lipid profile. Moreover, melatonin was further found to protect the activities of glycolytic, Krebs’ cycle, and ETC enzymes. Further, melatonin pre-treatment reduced the production of O2.− anion free radical and Ca2+ overload to protect the mitochondria at the ultrastructural level and reduced DNA damage to some extent. Therefore, this research strongly recommends melatonin as a therapeutic molecule against Cr-induced oxidative stress-mediated liver, heart, and kidney disorders.

Pharmacotherapeutic potential of malvidin to cure imidacloprid induced hepatotoxicity via regulating PI3K/AKT, Nrf-2/Keap-1 and NF-κB pathway

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine–aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions.

Pathological Effects of Aflatoxin on Hepatic Tissue of Rats, Experimental Study

The objective of studying this research is to discuss the pathological influence of aflatoxin on hepatic tissue. Aflatoxin was produced in this work using Aspergillus flavus. The samples were mixed with Potato Dextrose Agar (PDA) and left to incubate at a temperature of 28 ± 2°C for three to five days. We employed the fungal species for further usage once they were incubated. The AF was made via a fermentation process with Aspergillus parasitcus and rice, After the rice had fermented properly, it was steams to destroy the fungus, dried, and pulverised into a powder. The AF concentration in rice residue was determined using a TLC fluorometric densitometer on TLC spots. Ten rats from each of the two experimental groups—"G1 Control" (fed a baseline diet without AF) and "AF" (fed a different diet)—were randomly assigned to participate in the study. Group 2 rats were given 25 μg of AF daily. This study's duration was ninety days. Then, blood specimens were drawn by heart puncture using a syringe to determine serum enzyme levels. The animals were sacrificed in order to get tissue samples as well enzyme levels were assessed in serum specimens that had been centrifuged at 4000 × g for 15 minutes at 4 °C. The levels of AST, ALT, and GGT were determined using a spectrophotometer and a kit that was received from Biolabo. Liver samples were collected from rats after scarification, embedded in paraffin wax, and fixed with 10% neutralised formaldehyde. Hematoxylin and eosin were used for staining. The AF-treated group had substantially high levels of those enzymes compare to the control group (p < 0.05). G2 demonstrated that macrophage aggregations in the liver parenchyma constitute granulomatous lesions. Another portion showed hepatocyte apoptosis, which is defined by dense nuclei in the hepatocyte's irregular esonophilic cytoplasm, and a necrotic region with pyknosis or no nuclei at all. A portion of the liver of rats that were treated with aflatoxin showed proliferation of kupffer cells together with a few clusters of mononuclear cells around the major vein. In conclusion, Aflatoxin can affect of liver tissue histology as well as liver enzymes such as ALT, AST as well as GGT.

In Vitro Antitumor and Antioxidant Capacity as well as Ameliorative Effects of Fermented Kefir on Cyclophosphamide-Induced Toxicity on Cardiac and Hepatic Tissues in Rats.

Fermented prebiotic and probiotic products with kefir are very important to slow down and prevent the growth of tumors and to treat cancer by stimulating the immune response against tumor cells. Cyclophosphamide (CPx) is widely preferred in cancer treatment but its effectiveness in high doses is restricted because of its side effects. The aim of this study was to investigate the protective effects of kefir against CPx-induced heart and liver toxicity. In an experiment, 42 Wistar albino rats were divided into six treatment groups: the control (Group 1), the group receiving 150 mg/kg CPx (Group 2), the groups receiving 5 and 10 mg/kg kefir (Groups 3 and 4) and the groups receiving 5 and 10 mg/kg kefir + CPx (Group 5 and 6). Fermented kefirs obtained on different days by traditional methods were mixed and given by gavage for 12 days, while a single dose of CPx was administered intraperitoneally (i.p.) on the 12th day of the experiment. It was observed that alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB), ischemia modified albumin (IMA) and Troponin I values, which indicate oxidative stress, increased in the CPx-administered group, and this level approached that of the control in the CPx + kefir groups. Likewise, as a result of the kefir, the rats' CPx-induced histopathological symptoms were reduced, and their heart and liver tissue were significantly improved. In conclusion, it was observed that kefir had a cytoprotective effect against CPx-induced oxidative stress, hepatotoxicity and cardiotoxicity, bringing their biochemical parameters closer to those of the control by suppressing oxidative stress and reducing tissue damage.

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme‑oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Protective effects of cupressuflavone against doxorubicin-induced hepatic damage in rats

Doxorubicin (DOX) is a potent chemotherapeutic agent that is used in various sorts of malignancies. However, its uses are restricted owing to its deleterious effects on different organs including the liver. Cupressuflavone (CUP) is a plant-based flavonoid which is well known for its biological as well pharmacological potential. Our investigation aimed to evaluate the ameliorative potential of CUP against DOX provoked liver toxicity in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four distinct groups such as control, DOX (3 mg/kg), co- administrated DOX (3 mg/kg) + CUP (40 mg/kg) and CUP (40 mg/kg) only. DOX exposure reduced catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), Glutathione reductase (GSR), glutathione-S-transferase (GST) activities and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, the levels of ALT, AST and ALP were increased in response to DOX exposure. Furthermore, administration of DOX upregulated the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). The treatment of DOX reduced the levels of Bcl-2 while escalating the levels of Caspase-3, Caspase-9 and Bax. Similarly, DOX intoxication instigated various histopathological disruptions in hepatic tissues of rats. However, supplementation of CUP notably (p < 0.05) restored abovementioned hepatic dysregulations owing to its anti-oxidative, anti-inflammatory as well as anti-apoptotic potential. Our results manifested that CUP could be used as hepatoprotective agent againt DOX induced liver damage in rats.

The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.

Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats. 32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes. The liver catalase and MDA activity were elevated in the air pollution (p < .05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (p < .05). The SO2 group exhibited severe lesions in histopathology examinations. The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3.

The regulatory effects of pomiferin dietary on nickel-induced hepatic injury in Sprague–Dawley rats; action mechanisms and signaling pathways

The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague–Dawley rats received 10 mg/kg nickel chloride (NiCl2) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl2. Animals were anesthetized and livers were carefully collected to evaluate oxidative stress, inflammation, vascular injury, and hepatic function. Also, immunofluorescence analysis of apoptosis and DNA damage was performed on rat hepatic tissues. NiCl2 increased MDA production while reducing SOD, CAT, and GPx activity. NiCl2 induced the production of inflammatory cytokines and also platelet activation in hepatic tissue. Moreover, there were significant increases in AST, ALT, and LDH levels. NiCl2 also caused significant pathological changes in hepatic. Additionally, it remarkably induced up-regulations of apoptotic marker and 8-OHdG expressions by immunofluorescence labeling in liver cells. Whereas, pomiferin significantly attenuated lipid peroxidation and increased antioxidant defense system in liver. Also, the use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1β/IL-6. In addition, pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells. Pomiferin seems to counteract the deleterious effects of NiCl2 on hepatic tissue through different cellular and signaling mechanisms.

Sinensetin mitigates polystyrene nanoplastics induced hepatotoxicity in albino rats: A biochemical and histopathological study

Polystyrene nanoplastics (PS-NPs) are environmental pollutants that induce oxidative stress (OS) in multiple organs particularly, liver. Sinensetin (SNS) is a naturally present flavones that shows diverse pharmaceutical properties i.e., anti-oxidant, anti-inflammatory and anti-apoptotic. Therefore, the present study was designed to evaluate the therapeutic role of SNS against PS-NPs induced hepatotoxicity. 48 rats were distributed into 4 groups i.e., control, PS-NPs (50 µgkg−1) treated, PS-NPs + SNS (50 µgkg−1 + 20 mgkg−1) co-treated and only SNS (20 mgkg−1) treated group. PS-NPs intoxication reduced the activities of catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidases (GPx) glutathione reductase (GSR) and glutathione (GSH) level, whereas increased the levels of ROS and MDA. Additionally, PS-NPs increased the levels of liver serum marker enzymes i.e., alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Moreover, the level of inflammatory makers such as nuclear factor-kappa B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) activity were increased following the PS-NPS exposure. The intoxication of PS-NPs elevated Caspase-3, Bax and Caspase-9 levels, while reducing the Bcl-2 level. Furthermore, the exposure of PS-NPs induced significant histopathological damages in hepatic tissue of rats. However, the supplementation of SNS considerably improved the PS-NPs induced damages as well as histological changes due to its hepatoprotective, anti-inflammatory, anti-apoptotic and anti-oxidant nature.

Interactive effects of cadmium and titanium dioxide nanoparticles on hepatic tissue in rats: Ameliorative role of coenzyme 10 via modulation of the NF-κB and TNFα pathway

This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd2+) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd2+-induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd2+ (5 mg/kg b.wt), TNPs + Cd2+, or TNPs + Cd2++CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd2+ content were increased considerably in TNPs and/or Cd2+-exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd2+-exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd2+ on the liver. The study concluded that TNPs and Cd2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd2+ hepatotoxic impacts.

Bioactive compounds from the leaves of Maytenus ilicifolia Mart. ex Reissek: Inhibition of LDL oxidation, glycation, lipid peroxidation, target enzymes, and microbial growth

Ethnopharmacological relevanceMaytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds—terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. Aims of the studyWe aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. Materials and methodsOrganic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. ResultsHPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 μg/mL and 7.95 μg/mL) compared to acarbose (0.144 μg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. ConclusionThis study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.

Herb-drug interaction: Effect of sinapic acid on the pharmacokinetics of dasatinib in rats

Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph + ) acute lymphoblastic leukemia (ALL). DAS, a known potent substrate of cytochrome (CYP) 3A, P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) and is subject to auto-induction. The dietary supplementation of sinapic acid (SA) or concomitant use of SA containing herbs/foods may alter the pharmacokinetics as well as pharmacodynamics of DAS, that may probably lead to potential interactions. Protein expression in rat hepatic and intestinal tissues, as well as the in vivo pharmacokinetics of DAS and the roles of CYP3 A2 and drug transporters Pgp-MDR1 and BCPR/ABCG2, suggested a likely interaction mechanism. The single dose of DAS (25 mg/kg) was given orally to rats with or without SA pretreatment (20 mg/kg p.o. per day for 7 days, n = 6). The plasma concentration of DAS was estimated by using Ultra-High-Performance Liquid Chromatography Mass spectrometry (UHPLC-MS/MS). The in vivo pharmacokinetics and protein expression study demonstrate that SA pretreatment has potential to alter the DAS pharmacokinetics. The increase in Cmax, AUC and AUMC proposes increase in bioavailability and rate of absorption via modulation of CYP3 A2, PgP-MDR1 and BCPR/ABCG2 protein expression. Thus, the concomitant use of SA alone or with DAS may cause serious life-threatening drug interactions.

In Vitro Study on Spermicidal Action of Hydro-methanol Extract of Tinospora cordifolia (Willd.) Stem in Rat and Human Sperm: a Comparative Analysis.

Human fertility regulation is a major way to control overpopulation. In this perspective, this study emphasized the in vitro effect of hydro-methanol extract of Tinospora cordifolia (TCHME) stem for spermicidal and reproductive hypo-functions using human and rat samples. Control, 0.5-, 1-, and 2-mg TCHME-charged groups were considered to assess the relevant parameters. Levels of spermiological parameters like sperm motility, viability, the integrity of plasma and acrosomal membrane, and nuclear chromatin decondensation were significantly reduced (p < 0.05) in the dose- and duration-dependent TCHME-charged groups compared to the control. The inhibitory concentration 50 (IC50) of TCHME on motile human and rat sperms were 0.8 and 0.4 mg/ml, respectively. Testicular androgenic key enzymes and antioxidant enzymes (human sperm pellet, testes, and epididymis of rat)' activities were significantly diminished (p < 0.05), while antioxidant enzymes' activities were significantly elevated (p < 0.05) in renal and insignificantly (p > 0.05) elevated in hepatic tissues of rat in TCHME-charged groups compared to the control. Significant elevation (p < 0.05) of thiobarbituric acid reactive substances (TBARS)' level in human sperm pellet, testes, and epididymis of rats and significant diminution (p < 0.05) in TBARS levels of liver and kidney were observed in TCHME-charged groups. It focused that TCHME is more potent for stress imposition on reproductive tissues and sperm compared to the other tested tissues. Non-significant alterations (p > 0.05) in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the said organs of rat indicated its non-toxic effect. It highlighted that TCHME possesses spermicidal and reproductive tissue-specific effects which strengthen the possibilities of male contraceptive development from it.

Canagliflozin attenuates thioacetamide-induced liver injury through modulation of HMGB1/RAGE/TLR4 signaling pathways

Thioacetamide (TAA), a classic liver toxic compound, is used to establish experimental models of liver injury via induction of inflammation and oxidative stress. The current study was employed to explore the effects of canagliflozin (CANA), a sodium glucose cotransporter 2 (SGLT-2) inhibitor and antidiabetic agent, on TAA-induced acute liver injury. MethodsA rat model of acute hepatic injury was established using single intraperitoneal injection of TAA (500 mg/kg) and rats received CANA (10 and 30 mg/kg, orally) once daily for 10 days prior to TAA challenge. Liver function, oxidative stress, and inflammatory parameters were measured in serum and hepatic tissues of rats. ResultsElevated levels of liver enzymes, hepatic malondialdehyde (MDA), and serum lactate dehydrogenase (LDH) were significantly attenuated by CANA. CANA also increased hepatic superoxide dismutase (SOD) and glutathione (GSH). Hepatic levels of high-mobility group box 1 (HMGB1), toll like receptor4 (TLR4), receptor for advanced glycation end products (RAGE), and pro-inflammatory cytokines (IL-6, and IL-1β) were normalized with CANA. Additionally, Hepatic expression of p-JNK/p-p38 MAPK was significantly attenuated by CANA compared to TAA-treated rats. CANA also decreased hepatic immunoexpression of NF-κB and TNF-α and attenuated hepatic histopathological alterations via reduction of inflammation and necrosis scores and collagen deposition. Moreover, mRNA expression levels of TNF-α and IL-6 were reduced upon CANA treatment. ConclusionCANA attenuates TAA-prompted acute liver damage, via suppressing HMGB1/RAGE/TLR4 signaling, regulation of oxidative stress and inflammation pathways.

English

Cisplatin is an efficacious anticancerous chemotherapeutic agent that is used to cure multiple types of malignancies. However, it has several hazardous effects on multiple organs, particularly liver. Tectochrysin is a naturally occurring flavonoid with extensive pharmacological properties. In this research, the potential anti-oxidant properties of tectochrysin against cisplatin-triggered oxidative stress in rats’ hepatic tissues were investigated. 48 male albino rats were separated into 4 groups: control cisplatin (10 mg/kg), cisplatin + tectochrysin (10 mg/kg + 5 mg/kg), and tectochrysin (5 mg/kg). The trial executed for one month. The biochemical, inflammatory, histopathological and liver markers were evaluated. The results of the research suggested that cisplatin treatment remarkably lowered the activities of glutathione (GSH), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GPx) as well as catalase (CAT) while escalated malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Cisplatin administered rats exhibited significantly higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) levels. Furthermore, cisplatin administration significantly elevated the inflammatory indicators i.e., interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) as well as nuclear factor kappa-B (NF- κB) and cyclooxygenase-2 (COX-2) activity along with histopathological impairments. Conversely, co-administration with tectochrysin effectively reversed the cisplatin-triggered impairments and abnormalities in the hepatic tissue of rats. The current investigation demonstrated that tectochrysin lowered cisplatin-induced hepatotoxicity owing to its antioxidant, reactive oxygen species scavenging activities and anti-inflammatory effects

A Comparative Study on GC-MS Profiles and Effect of Ethanolic Extracts of Stem-Bark and Leaves of Daniellia oliveri on Cerebral Sodium Pump and Thiols Status in Fenton Reaction Treated Rat Organs In-vitro

Daniellia oliveri is one of the most extensively utilized medicinal plants in Nigeria and some West African countries for the treatment of various ailments. In the present study, the GC-MS profiles and effect of ethanolic extracts of stem bark and leaves of Daniellia oliveri on lipid peroxidation, Na+/K+-ATPase activity and thiols status in H2O2 and Fe2+ (fenton reaction) assaulted cerebral and hepatic tissue homogenates was investigated. The stem bark and leaves were extracted with absolute ethanol for 72hrs and concentrated in a rotary evaporator. Wistar rats were euthanized and the brains and livers were removed, homogenized, centrifuged and the supernatants were used for lipid peroxidation, Na+/K+-ATPase activity, and thiol assays in the presence of prooxidants (1mM H2O2 or 10μM Fe2+ or H2O2 and Fe2+).The results revealed that ethanol extract of both the leaf and stem-bark inhibited lipid peroxidation induced by H2O2, Fe2+ and combination of H2O2 and Fe2+ and this was evident in the reduction of lipid peroxidation adducts formation in rat liver and brain homogenates with the stem-bark possessing more efficacy. Furthermore, the results of Na+/K+-ATPase and thiol assays revealed that H2O2 and Fe2+ inhibited the activity of cerebral Na+/K+-ATPase, while H2O2/Fe2+ caused a marked reduction in the levels of both protein and non-protein thiols in the tissues homogenates. However, the ethanolic extract of Daniellia oliveri extirpated this anomaly by increasing the activity of cerebral Na+/K+-ATPase as well as the thiol level in the rat hepatic and cerebral tissues. Finally, GC-MS analysis was carried out on the ethanolic extracts of the stem bark and leaves of Daniellia oliveri and results revealed the presence of 21 compounds including 1,2-Benzisothiazol-3-amine, 1H-Indole-2-carboxylic acid, 2-Ethylacridine, Ethyl 2-(2-chloroacetamido)-3,3,3-trifluoro-2-(3-fluoroanilino) propionate and trans-1-Butyl-2-methylcyclopropane in the stem bark and 10 compounds including Methylthio-acetonitrile, 2-Methyl-Z,Z-3,13-octadecadienol, Desulphosinigrin and 4H-1,2,4-triazole-3,5-diamine in the leaves, justifying the observed biological activities of Daniellia oliveri and the higher potency of the stem bark may be attributed to the presence of more bioactive constituents found in it. This study therefore justifies the medicinal usage of leaves and stem-bark of Daniellia oliveri and suggests its consideration in the treatment and management of degeneration diseases with etiology associated with oxidative stress.

WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-β/β-catenin/α-SMA pathway

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-β/β-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat’s survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-β, β-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats’ survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-β, β-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

Ethanol Extract of Curcuma longa L. Protects Against Carbon Tetrachloride-Induced Oxidative Damage in Renal and Hepatic Tissues of Rats

Ethanol Extract of Curcuma longa L. Protects Against Carbon Tetrachloride-Induced Oxidative Damage in Renal and Hepatic Tissues of Rats

Antioxidative effect of metformin on valproic acid induced hepatoxicity in male rats

Metformin is 1,1-dimethylbiguanide hydrochloride, is the first-line therapy for type 2 diabetes. Additionally, several studies focused on the role of metformin in antioxidant activities for the treatment of hepatic disorders. The experimentally&#x0D; &#x0D; -based result on valproic acid's liver injury, a front-line medicine for the treatment of epilepsy, attracted a lot of interest. As a result, the effect of metformin on valproic acid-induced redox disturbances in rat hepatic tissue was studied. metformin at 250 mg/kg dose was administered via oral gavage for 30 days, and valproic acid at a dose of 400 mg/kg was administered by intraperitoneal route starting from the twenty-second day of the experiment, for eight days to induce hepatotoxicity. Treatment with metformin reduced valproic acid-enhancing alanine aminotransferase, aspartate aminotransferase activities. Tissue levels of malondialdehyde in the liver tissue of valproic acid-treated rats significantly increased (P-value &lt; 0.05) whereas glutathione decreased. The coadministration of metformin with valproic acid significantly decreased the malondialdehyde levels and increased glutathione levels (P-value &lt; 0.05). Finally, metformin protected rats from valproic acid-induced hepatotoxicity, improved antioxidant status, and reduced hepatic oxidative stress.