Liver Function Enzymes Research Articles

Toxicity Status of Nano Powder of Stem Bark of <i>Bauhinia Variegata</i> Linn. on Experimental Animals

The assumption that medicinal plants are less toxic or cause fewer adverse effects due to their natural composition is debatable. Hence, this study was conducted to evaluate the safety and toxicity of Nano Kanchanara stem bark powder (NKSP) on liver function. The oral acute toxicity of NKSP was conducted in accordance with OECD Guidelines 423 and was carried out with six (6) female Wistar albino rats, divided into two groups of three rats each. Test rats were orally administered a single dose of 2000 mg/kg of NKSP and were observed for changes in behavior and mortality for the next 14 days, while the Control Group was given feed and water ad libitum. The data obtained from the oral acute toxicity study indicated that there were non-significant (P<1.000) decreases in body weight of rats in the treatment groups of NKSP at 2000 mg/kg. There were no elevations in specific liver function enzymes, whereas there were increases in serum SGOT, SGPT, and albumin levels. Plasma total proteins and globulin, total bilirubin and serum creatinine were within the normal range. Albeit, hydropic changes and steatosis in liver lesions at NKSP 2000 mg/kg. The study suggests that oral administration of NKSP is safer at dose levels less than 2000 mg/kg/day.

Activation of AMPK Entails the Protective Effect of Royal Jelly against High-Fat-Diet-Induced Hyperglycemia, Hyperlipidemia, and Non-Alcoholic Fatty Liver Disease in Rats.

This study examined the mechanism underlying the protective effect of royal jelly (RJ) against high-fat-diet (HFD)-mediated non-alcoholic liver disease (NAFLD) in rats. Adult male rats were divided into five groups (n = 8 each): control fed a standard diet, control + RJ (300 mg/kg), HFD, HFD + RJ (300 mg/kg), and HFD + RJ + CC (0.2 mg/kg). The treatment with RJ reduced weight gain, increased fat pads, and attenuated fasting hyperglycemia, hyperinsulinemia, and glucose tolerance in the HFD-fed rats. It also reduced the serum levels of liver function enzymes, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin but significantly increased the serum levels of adiponectin. In addition, and with no effect on lipid excretion in stool, RJ significantly decreased the hepatic mRNA expression of SREBP1, serum, hepatic cholesterol, and triglycerides but increased hepatic mRNA levels of PPARα. Furthermore, RJ reduced the hepatic levels of TNF-α, IL-6, and malondialdehyde (MDA) in the livers of these rats. Of note, with no effect on the mRNA levels of AMPK, RJ stimulated the phosphorylation of AMPK and increased the levels of superoxide dismutase (SOD) and total glutathione (GSH) in the livers of the control and HFD-fed rats. In conclusion, RJ attenuates NAFLD via its antioxidant potential and adiponectin-independent activation of liver AMPK.

Origanum majorana L. extract alleviates dexamethasone-induced hepatotoxicity, oxidative stress and pathological alterations in vivo

BackgroundOriganum majorana (O. majorana) is one of the most widely used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, antimutagenic, anticoagulant and beneficial properties. Our study's main goal is to determine how well O. majorana leaf extract can reduce hepatotoxicity and oxidative stress produced by dexamethasone (DXM). Thirty female rats were divided into three groups of ten. Animals in group1 received distilled water daily for eight weeks and served as control. Those in group 2 exposed subcutaneously to 0.1 mg/kg body weight of DXM three times per week for eight weeks and served as the toxic group, while those in group 3 were treated daily and orally with 100 mg/kg of O. majorana aqueous extract + 0.1 mg/kg of DXM three times per week for eight weeks and served as treated group.ResultsDue to DXM treatment, the activities of liver function markers were significantly elevated (P < 0.0001), whereas O. majorana pretreated animals improved or reduced the elevated liver function enzyme activities. Dexamethasone administration considerably enhancing oxidative stress which rose (P < 0.0001) MDA concentration and attenuated the antioxidant defense system by decreasing the activities of GST, GSP, GSR, and CAT significantly in liver homogenate when compared to control animals. The results further demonstrated that pretreatment with O. majorana boosted the antioxidant defenses against the damaging effects of DXM.ConclusionIt can be said that dexamethasone exposure induced- hepatotoxicity and oxidative stress in rats that repaired by O. majorana aqueous extract which had the ability to reduce the impact of hepatic damage. To evaluate the health benefits and safety of O. majorana in individuals, more clinical research is needed.Graphical abstract

Chronic cold-stress induced histopathological changes, oxidative stress, and alterations in liver functions and nutrient composition of hybrid red tilapia and the potential protection of unsaturated fatty acids

The hybrid red tilapia (♂Oreochromis niloticus × ♀O. mossambicus) is a promising tilapia fish with high growth rate, market acceptability, and the ability to live in a wide range of salinities, but it is sensitive to low water temperature. Therefore, the objective of this experiment was to improve hybrid red tilapia resistance to chronic cold stress by increasing unsaturated fatty acids and evaluating their effects on fish body weight, hepatosomatic index (HSI), body nutrient composition, liver function enzymes, histopathological alterations, and biomarkers of oxidative stress in the gills and liver. For 98 days, fish were fed four diets based on two dietary fat sources: corn oil (a traditional source) and Aquafat-O® (a commercial product rich in high polyunsaturated fatty acids), in different ratios of 3:0 (T0), 2:1 (T1), 1:2 (T2), and 0:3 (T3), respectively. Subsequently, all groups (T0+, T1, T2, and T3) were subjected to water cold stress at 13 °C for 15 days, with half of the control group serving as a negative control (T0-; at a rearing water temperature of 25-26 °C). Chronic old stress caused significant reductions in fish body weight, HSI, aspartate transaminase and alanine transaminase activities, fat and energy contents, and oxidative stress biomarkers in the liver and gills. Red tilapia subjected to low temperatures showed severely altered histopathological conditions in the liver and gills. However, by gradually increasing the Aquafat-O® ratio in the diet, the negative effects of cold stress were mitigated. Thus, it could be concluded that the beneficial use of Aquafat-O® (as a promising fat source) at a percentage of up to 69.60 g kg-1 is necessary to cope with the cold-water stress for sensitive hybrid red tilapia.

Studying the actions of sage and thymoquinone combination on metabolic syndrome induced by high-fat diet in rats.

High-fat diet is one of the most imperative risk factors for cardiovascular disorders. Thymoquinone (TQ) is one of the active pharmacological components of Nigella sativa (black cumin). Salvia officinalis L. (sage) has been demonstrated to have diverse pharmacological actions. The main objective of this study was to determine the effects of sage and TQ combination on hyperglycemia, oxidative stress, blood pressure, and lipid profile in rats fed with a high-fat diet (HFD). Wistar male rats were divided into five groups; normal diet (ND) and HFD, in which rats were fed with a normal diet or HFD for 10 weeks, respectively. In HFD + sage group, animals were administered sage essential oil (0.052 ml/kg) orally along with HFD. In HFD + TQ group, rats were administered TQ (50 mg/kg) orally with HFD. In HF + sage + TQ group, animals received sage + TQ along with HFD. Blood glucose (BGL) and Fast serum insulin (FSI) levels, oral glucose tolerance test, blood pressure, liver function tests, plasma, and hepatic oxidative stress markers, antioxidant enzymes, and glutathione content, and lipid profile were measured. Sage and TQ combination decreased the final body weight, weight gain, BGL, FSI, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The combination also lowered systolic and diastolic arterial pressures and liver function enzymes. The combination deterred lipid peroxidation, advanced protein oxidation product, and nitric oxide amplification, as well as restoring the superoxide dismutase, catalase activities, and glutathione content in plasma and hepatic tissue. Sage and TQ combination reduced the plasma total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels and amplified high-density lipoprotein (HDL). The results of the current study verified that sage essential oil, together with TQ exhibited hypoglycemic, hypolipidemic, and antioxidant actions and thus could be a valuable addition to diabetes management.

Effects of dietary walnut (Juglans regia) leaves extract on immunity, gene expression responses, and disease resistance in Oreochromis niloticus

The dietary effects of walnut leaf extract (WLE) on the growth, immunity, and resistance of Oreochromis niloticus to bacterial infection have been investigated. Five diets were prepared with various WLE doses of 0, 250, 500, 750, and 1000 mg/kg, termed as Con (control), WLE250, WLE500, WLE750, and WLE1000, respectively. Fish (11.67 ± 0.21 g) were fed these diets for 60 days and then challenged with Plesiomonas shigelloides. Before the challenge, it was observed that dietary WLE did not significantly affect the growth, blood proteins (globulin, albumin, and total protein), and liver function enzymes (ALT and AST) activities. The WLE250 group significantly increased serum SOD and CAT activities more than other groups. The serum immunological indices (lysozyme and myeloperoxidase activities) and hematological parameters (phagocytic activity %, phagocytic index, respiratory burst activity, and potential activity) were significantly increased in the WLE groups compared with the Con group. The expression of IgM heavy chain, IL-1β, and IL-8 genes were significantly upregulated in all WLE-supplemented groups in comparison with the Con group. The fish survival rates (SR; %) post challenge in the Con, WLE250, WLE500, WLE750 and WLE1000 groups were 40.0%, 49.3%, 86.7%, 73.3%, and 70.7%, respectively. The Kaplan–Meier survivorship curves illustrated that the highest SR% was found in the WLE500 group (86.7%) amongst the other groups. Accordingly, we can suggest that feeding O. niloticus with a diet supplied with WLE at a dose rate of 500 mg/kg over 60 days could enrich haemato-immune responses and increase the fish survival against the challenge with P. shigelloides. These results recommend using WLE as a herbal dietary supplement to substitute antibiotic use in aquafeed.

Abstract Number ‐ 226: Pontine Stroke Presenting as 1.5 Syndrome Evolving to 9 Syndrome over 72 Hours.

Introduction A 75 year old woman with a past medical history of hypertension developed sudden‐onset vertigo, nausea and vomiting. She did not immediately seek medical care, thinking she was suffering from food poisoning. The following day her symptoms improved however she developed new right sided weakness and gait imbalance, prompting her presentation to the ED. Her neurologic exam noted complete loss of adduction of the right eye and loss of horizontal extraocular movements of the left eye. She also displayed right upper extremity paresis, right upper extremity dysmetria and mild dysarthria. MRI of the brain disclosed acute pontine infarcts in the ventral and dorsal left paramedian regions. Over the next three days, her horizontal gaze palsy improved with some return of adduction of the right eye and horizontal movements of the left eye. However right sided paresis worsened, and in addition, progressed to include complete left facial palsy (lower motor neuron lesion). She was able to be discharged to rehab, placed on Aspirin 81 mg daily and Ezetimibe (due to elevated liver function enzymes) and 30 day Cardiac Event Monitor follow up. Methods Case report and review of literature. Results Due to the combination of multiple cranial nuclei and white matter tracts in the brainstem, ischemia can lead to several clinical manifestations. There are various presenting clinical syndromes, named numerically by structures involved and/or the clinical deficit. One‐and‐a‐half (1.5) syndrome, first reported by Fischer in 1967, is an uncommon entity caused by a lesion (most commonly infarction) in the pontine tegmentum [1]. It consists of complete ipsilateral horizontal gaze palsy (due to involvement of ipsilateral Paramedian Pontine Reticular Formation/Abducens Nucleus and Medial Longitudinal Fasciculus) and loss of adduction of the contralateral eye (due to involvement of the contralateral Medial Longitudinal Fasciculus). Extension of the lesion to the facial nucleus can produce ipsilateral lower motor neuron type facial palsy, leading to an even more uncommon 8.5 syndrome (7 + 1.5), described by Eggenberger in 1998 [2]. When the lesion involves the corticospinal tracts and/or the medial lemniscus, it can lead to contralateral hemiparesis and/or hemisensory deficits; the so called “9 syndrome” first proposed by Rosini et al in 2013 [3]. This rare entity has been reported in only a handful of cases. Conclusions The awareness of complex brainstem neuroanatomy enables precise localization of the clinical deficits. The noted slow progression of the clinical syndrome from 1.5 to 8.5 and finally 9 syndrome over 72 hours in this case highlights the complexity of small vessel brainstem ischemia.

The anti-toxic effect of the date palm fruit extract loaded on chitosan nanoparticles against CCl4-induced liver fibrosis in a mouse model

The liver is the most important organ in the body. Hepatocyte oxidative damage occurs to excess ROS. Liver fibrosis is a mechanism that the immune system uses to treat extreme inflammation by repairing damaged tissue with the creation of a scar. The outcome of fibrosis may be reversed by consuming natural plant extracts with high ROS-scavenging ability. The date palm fruits contain caffeic acid, gallic acid, syringic acid, and ferulic acid, which have anti-inflammatory, antioxidant, and hepatoprotective properties. This study aimed to prepare a date fruit extract, load it onto chitosan nanoparticles, and compare its anti-fibrotic activity with the unloaded crude extract in the CCl4-mouse model. Our findings show that nanocomposite (Cs@FA/DEx) has anti-fibrotic properties and can improve liver function enzymes and endogenous antioxidant enzymes by inhibiting cell apoptosis caused by CCl4-induction in mice. Furthermore, significantly reduced CD95 and ICAM1 levels and down-regulation of TGFβ-1 and collagen-α-1 expression demonstrated the anti-fibrotic effects of the Cs@FA/DEx. Therefore, the Cs@FA/DEx might be an innovative supplement for inhibiting liver fibrosis and hepatocyte inflammation induced by chemical toxins. Besides, this nano-supplement could be a promising anti-hepatocellular carcinoma agent as it has potent in vitro anticancer activity against the HePG2 cell line.

A novel mechanistic approach for the anti-fibrotic potential of rupatadine in rat liver via amendment of PAF/NF-ĸB p65/TGF-β1 and hedgehog/HIF-1α/VEGF trajectories

Hepatic fibrosis is one of the major worldwide health concerns which requires tremendous research due to the limited outcomes of the current therapies. The present study was designed to assess, for the first time, the potential therapeutic effect of rupatadine (RUP) in diethylnitrosamine (DEN)-induced liver fibrosis and to explore its possible mechanistic actions. For the induction of hepatic fibrosis, rats were treated with DEN (100 mg/kg, i.p.) once weekly for 6 consecutive weeks, and on the 6th week, RUP (4 mg/kg/day, p.o.) was administered for 4 weeks. Treatment with RUP ameliorated changes in body weights, liver indices, liver function enzymes, and histopathological alterations induced by DEN. Besides, RUP amended oxidative stress, which led to the inhibition of PAF/NF-κB p65-induced inflammation, and, subsequently, prevention of TGF-β1 elevation and HSCs activation as indicated by reduced α-SMA expression and collagen deposition. Moreover, RUP exerted significant anti-fibrotic and anti-angiogenic effects by suppressing Hh and HIF-1α/VEGF signaling pathways. Our results highlight, for the first time, a promising anti-fibrotic potential of RUP in rat liver. The molecular mechanisms underlying this effect involve the attenuation of PAF/NF-κB p65/TGF-β1 and Hh pathways and, subsequently, the pathological angiogenesis (HIF-1α/VEGF).Graphical abstract

Oliveria decumbens Extract Exhibits Hepatoprotective Effects Against Bile Duct Ligation-Induced Liver Injury in Rats by Reducing Oxidative Stress

Background: Cholestasis is described as a disease in which bile flow from the liver is reduced or stopped, and due to its oxidative effects, irreversible consequences may occur. Objectives: Due to the remarkable antioxidant properties of Oliveria decumbens (OD) and the contribution of oxidants to the progression of bile duct ligation (BDL)-induced cholestasis, this research aimed to examine how the OD ethanolic extract affected liver damage and oxidant-antioxidant balance markers in BDL-induced cholestasis. Methods: Forty male Wistar rats weighing 200 - 250 g were used. Cholestasis was induced using the BDL approach. The rats were categorized into four groups: Group 1, sham-control (SC); group 2, cholestatic; group 3, SC + OD; and group 4, cholestatic + OD. A dose of OD ethanolic extract was administered orally (500 mg/kg/day) to rats for seven days. Seven days following surgery, the rats’ blood samples were collected; after sacrifice, a part of the liver tissue was isolated. A histopathological examination was performed, while the rest was stored at -70°C in liquid nitrogen. Heparin-containing tubes were used to gather blood samples. In plasma and hepatic tissue, biochemical tests, histopathological evaluations, and oxidative stress markers staining levels were performed. Results: Our findings showed that OD could effectively reduce liver injury by reducing the activity of liver function enzymes (AST and ALP). At the same time, it did not affect total bilirubin and protein. Bile duct ligation-induced hepatic markers of protein oxidation (PCO) and reactive nitrogen species (NO) were significantly decreased by OD, and it also promoted liver antioxidant capacity by enhancing superoxide dismutase (SOD) activities. Moreover, OD treatment prevented liver bile duct proliferative changes in histopathologic analysis. Conclusions: Our study confirmed that OD exerts substantial hepatoprotective activities against BDL-induced cholestasis by improving liver damage markers and regulating oxidative stress. It may be a beneficial therapeutic agent for managing cholestasis. Bioassay-guided isolation and identification of bioactive OD secondary metabolites can further direct the discovery of potential natural-based drug candidates.

Effects of kiwi fruit (Actinidia chinensis) polysaccharides on metabolites and gut microbiota of acrylamide-induced mice.

Kiwifruit (Actinidia chinensis) has rich nutritious and medicinal properties. It is widely consumed worldwide for the intervention of metabolism disorders, however, the underlying mechanism remains unclear. Acrylamide, a well-known toxic ingredient, mainly forms in high-temperature processed carbohydrate-rich food and causes disorders of gut microbiota and systemic metabolism. This study explored the protective effects and underlying mechanisms of kiwifruit polysaccharides against acrylamide-induced disorders of gut microbiota and systemic metabolism by measuring the changes of gut microbiota and serum metabolites in mice. The results showed that kiwifruit polysaccharides remarkably alleviated acrylamide-induced toxicity in mice by improving their body features, histopathologic morphology of the liver, and decreased activities of liver function enzymes. Furthermore, the treatment restored the healthy gut microbiota of mice by improving the microbial diversity and abundance of beneficial bacteria such as Lactobacillus. Metabolomics analysis revealed the positive effects of kiwifruit polysaccharides mainly occurred through amino and bile acid-related metabolism pathways including nicotinate and nicotinamide metabolism, primary bile acid biosynthesis, and alanine, aspartate and glutamate metabolism. Additionally, correlation analysis indicated that Lactobacillus exhibited a highly significant correlation with critical metabolites of bile acid metabolism. Concisely, kiwifruit polysaccharides may protect against acrylamide-induced toxicity by regulating gut microbiota and metabolism.

Royal Jelly bioactive compounds and exercise improved cardiomyopathy and redox status in patients under methadone maintenance therapy: Randomized clinical trial

BackgroundDrug abuse is one of the world's most significant health policy concerns. Long-time opium use is significantly associated with the incidence of coronary artery disease and altered liver enzyme concentration and function. MethodsIn this randomized clinical trial, 80 men addicted to opium and who underwent methadone maintenance therapy (MMT) were randomized to four groups, including the control group, cases that performed resistance band exercise, cases that consumed Royal Jelly, cases that performed resistant band exercise and consumed Royal Jelly (100 mg/kg). Serum levels of antioxidative, cardiac, and liver function were measured at the baseline and end of the study (eight weeks). The vital proteins were screened by in silico analysis. Moreover, the authors found 18 microRNAs with a significant differential expression in the addiction status as dynamic monitoring biomarkers. ResultsThe concentration of the catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were significantly increased in men who performed exercise and consumed Royal Jelly (RJ+EX) compared with the other groups. Moreover, we found that cardiac and liver function concentrations such as troponin-1, malondialdehyde, creatine kinase, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase were improved in the RJ+EX group. ConclusionArtificial intelligence and experimental tests concluded that consuming Royal Jelly and regular exercise training programs might be the adjunct protocol to MMT, improving quality of life and side effects of methadone therapy.

Effect of wheat germ oil on phenylhydrazine-induced toxicity in male albino rats

Wheat germ oil (WGO) is a natural source of antioxidant such as glucosylated hydroquinones, tocopherols and it is an excellent source of polyunsaturated fatty acids. The point of the present study is to see how efficient is the WGO against phenylhydrazine (PHZ) induced hemotoxicity in rats. Rats were divided into five groups (six rats each); control group (normal rats), WGO group (administrated by daily oral dose of WGO, 300 mg/kg b.w.), PHZ group (injected intraperitoneally with a daily dose of PHZ, 60 mg/kg b.w. for 3 consecutive days), treated group (injected with PHZ then after 3 days administered by WGO) and protective group (administrated daily by WGO for 11 days then injected with PHZ). The experimental trial was continued for a total period of 14 days. The results showed that the PHZ induced significant decreases in hematological parameters (RBCs, Hb, Hct, PLT), serum proteins (total protein, albumin and globulin) and antioxidant enzymes (CAT, GPX and SOD) activity and significant increases in white blood cells (WBCs), erythropoietin hormone, serum ferritin level, serum liver function parameters (ALT, AST, TBIL and ALP), serum kidney function parameters (creatinine, urea and uric acid) and malondialdehyde (MDA) content. Administration of WGO improved the hematological parameters, erythropoietin hormone, ferritin level, serum proteins, liver function enzymes, kidney function parameters, antioxidant enzyme activities and MDA content in rats injected with PHZ. In conclusion, the results of the present study revealed that the WGO has a therapeutic and protective roles in improving the hemolytic anemia and toxicity induced by PHZ.

Sinapic acid attenuates cyclophosphamide-induced liver toxicity in mice by modulating oxidative stress, NF-κB, and caspase-3.

Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties. The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Methanolic extract of S. securidaca flowers, leaves, and seeds' antihyperlipidemic effects on high fat diet-induced hyperlipidemia in Wistar rats.

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

ROLE OF DIMETHYL FUMARATE (NRF2 ACTIVATOR) IN REDUCING OF CIPROFLOXACIN-INDUCED HEPATOTOXICITY IN RATS VIA THE NRF2/HO-1 PATHWAY.

The aim: The present study aims to study the effect of DMF on ciprofloxacin-induced liver damage as assessed by liver function and liver pathology and to study this effect if it is thought to activate the Nrf2 antioxidant defense mechanism. Materials and methods: G1 (control), G2 (ciprofloxacin group), G3 and G4 (two DMF groups rats treated with DMF 50mg and 100mg), and G5 and G6 (two DMF groups rats treated with DMF 50mg and 100mg) (two ciprofloxacin Plus DMF at 50 mg and 100 mg). The tests included study of liver function, Nrf2 analysis, and anti-oxidant enzyme analysis. Results: The serum blood Nrf2, HO-1, and tissue anti-oxidant enzymes all increased after ciprofloxacin treatment. The serum levels of Nrf2 and HO-1 were higher in the ciprofloxacin plus DMF groups, but anti-oxidant enzymes were lower. DMF increased Nrf2 expression in rats when ciprofloxacin caused hepatotoxicity. Conclusions: DMF lowers experimental hepatotoxicity in vivo. This effect is thought to activate the Nrf2 antioxidant defense mechanism.

Serum Biochemical Changes among Chronic Kidney Disease Patients in a Rural Cohort of Odisha, India: A Cross-sectional Study

Introduction: Chronic Kidney Disease (CKD) is one of the fastest-growing causes of death worldwide. Monitoring biochemical parameters such as liver function tests, kidney function tests, and lipid profiles is crucial for early identification of health complications, prevention, and prompt management in CKD patients. Aim: To investigate the association of sociodemographic factors and serum biochemical indicators with Glomerular Filtration Rate (GFR) among CKD patients in rural Odisha, India. Materials and Methods: A cross-sectional study was conducted in a rural cohort of the Model Rural Health Research Unit (MRHRU) established in Cuttack district, Odisha, India, from March 2021 to April 2021. A total of 530 registered CKD patients were enrolled in the study. Sociodemographic data and blood samples were collected for lipid profile, kidney function, and liver function analysis. The data were analysed using STATA 15.1 and RStudio 2021.09.0+351. Results: The mean age of the study participants was 51.2±14.1 years, with 330 (62.26%) being male. A total of 74% of the participants showed abnormal Estimated Glomerular Filtration Rate (eGFR). Abnormal eGFR was found to be more common among the older age group (&gt;45 years), those who were literate, and those in private jobs, compared to their counterparts. Both lipid profile and liver function abnormalities were significantly associated with individuals having normal eGFR. Conclusion: The positive association of eGFR with lipid profile and liver function enzymes highlights the importance of regular screening of these parameters among CKD patients for early prevention and control of future complications.

Prevalence of Hepatitis D Virus among People Attending the Antiretroviral Clinic and the Effect on the Liver Function Enzymes

Hepatitis D virus is an incomplete RNA virus requiring the assistance of the hepatitis B virus, specifically the HBsAg, to be infectious in humans. This study was designed to determine the prevalence of HDV among HIV patients and the effect on liver enzymes. The study was conducted at the Rivers state University Teaching hospital, Port Harcourt, Rivers State. Blood samples were obtained through vein puncture from 93 adults of which 41(44%) were males while 52(56%) were females between the ages 18 and 70 years attending the antiretroviral clinic and CD4+ cell count was also obtained. The samples were preserved at -20ºC. Each of the samples was tested using a SWE-Care rapid strip (China) for the presence of HBsAg. HDV antibody was detected using a Dia. Pro ELISA kit (Italy). The AST, ALT and ALP were determined. SPSS 21 was used to analyze the data and P values were determined. From the total samples collected, 7(7.5%) of them were positive to the HBsAg test of which 3(3.2%) were males, while 4(4.3%) of them were females. Of the 7 people positive to the HBsAg, 6(6.4%) were positive to the HDV antibody with 3(3.2%) females and 3(3.2%) males. There was significant depletion of the CD4+ cells across the groups. For the liver function test, the P values were ˃ 0.05 for AST, ALT and ˂ 0.05 for ALP. The HDV infection from the study was not gender, nor age based and suggests a negative impact on the CD4 cells. The liver function enzyme analysis, suggest higher risk of hypertension in HIV/HBV/HDV infection.

Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model.

Alcohol-induced oxidative stress is a key player in the development of liver diseases, and herbal alternatives are important means of ameliorating the hepatotoxic effects. The study aimed to evaluate the hepatoprotective potentiality of Artabotrys odoratissimus, an important medicinal shrub from the family Annonaceae. The phenolic compounds from bark ethanol extract (BEE) were detected using RP-HPLC. The in vitro hepatoprotective activity against ethanol-induced damage was studied in HepG2 cells with cell viability assays, mitochondrial membrane potential (MMP) assay, reactive oxygen species (ROS) assay, double staining assay and western blotting. The in vivo mice model was used to evaluate the alcohol-induced stress with liver function enzymes, lipid profile and histopathology. All the thirteen phenolic compounds detected with HPLC were docked onto protein targets such as aspartate amino transferase (AST), alkaline phosphatase (ALP) and inducible nitric oxide synthase (NO). The RP-HPLC detected the presence of various phenolics including rutin, chlorogenic acid and catechin, amongst others. Co-administration of BEE with ethanol alleviated cell death, ROS and MMP in HepG2 cells compared to the negative control. The extract also modulated the MAP kinase/caspase-3 pathway, thereby showing protective effects in HepG2 cells. Also, pre-treatment for 14days with the extract in the mice model before a single toxic dose (5g/kg body weight) reduced the liver injury by bringing the levels of liver function enzymes, lipid profile and bilirubin to near normal. In silico analysis revealed that rutin showed the best binding affinity with all the target proteins in the study. These results provide evidence that BEE possesses significant hepatoprotective effects against ethanol-induced oxidative stress in hepatic cells and in vivo models, which is further validated with in silico analysis.

Antitrypanosomal activity of Argemone mexicana extract and fractions in the animal model of Trypanosoma brucei brucei infection

Abstract Background This study investigated the antitrypanosomal activity of Argemone mexicana extract and fractions in the animal model of Trypanosoma brucei brucei infection. Methods The whole plant was cold-macerated with methanol. The liquid–liquid partitioning of the extract with n-hexane, ethyl acetate, butanol, and water produced various fractions of the extract. Infection was established by the inoculation of T. brucei brucei-infected red blood cells in the animals. Treatment with the extract and fractions was done orally for 5 days postinfection at 200 and 400 mg/kg doses. Diminazene aceturate 3.5 mg/kg and 5 mL/kg 10% Tween 80 served as standard and vehicle control, respectively. Parasite load, packed cell volume (PCV), animal body weight, and survival as well as serum liver function enzymes’ activities were also assessed. Results The extract and the n-hexane fraction showed the presence of all the tested phytocompounds except tannins and cardiac glycosides, respectively. The extract showed a reduction in parasitemia while the order of activity for the fractions was n-hexane ≫ water ≫ butanol ≫ ethyl acetate. The n-hexane fraction produced complete protection against parasite-induced mortality just like the reference standard and a higher increase in PCV compared with the reference standard. The extract, n-hexane, and water fractions showed protection against infection-induced liver damage with a significant (P &lt; 0.05) difference when compared to the vehicle control group. Conclusion A. mexicana showed antitrypanosomal activity which may be attributed to the presence of phytocompounds particularly saponins, which were present in the extract and fractions that showed antitrypanosomal activity but absent in fractions that showed no or weak antitrypanosomal activity.