Cytokine profile as biomarker of COVID-19 and its correlation with liver function enzymes and other markers of inflammation

Introduction and Aim: Various hematological and biochemical parameters are assessed as biomarkers of COVID-19, caused by the SARS-CoV-2. In this study, efforts were made to identify the correlation of cytokines (IL-6, TNF-?, IL-1?, and IL-1?) with the liver function enzyme markers, LDH, CRP, Ferritin, and D-dimer. We also assessed the correlation of cytokines with severity of COVID-19. Materials and Methods: We analyzed 53 serum samples of RT-PCR-positive patients admitted to the hospital. Cytokines (IL-6, TNF-?, IL-1?, and IL-1?) were analyzed with sandwich ELISA. The levels of cytokines were compared between mild, moderate, and severe cases of COVID-19, and the correlation among cytokines, liver function marker enzymes, LDH, CRP, D-dimer, and ferritin were analyzed. Results: Along with CRP, LDH and ferritin, IL-6 showed significant difference between mild, moderate, and severe COVID groups. significant correlation between IL-6 & LDH (p -.002), IL-6 & D-Dimer (p- .010), IL-6 & IL-1? (p- .027), IL-1? & D-Dimer (p- .010), IL-1? & LDH (p-.027), and IL-1? & TNF-? & (p-.000). Conclusion: Cytokines especially IL-6 correlated with disease severity. Assaying the profile of cytokines could be of immense value in diagnosis, prognosis, and management of COVID-19.

Ilex paraguariensis extract as an alternative to pain medications

Pain is a common and distressing symptom of many diseases and its clinical treatment generally involves analgesics and anti-inflammatory drugs. This study evaluated the toxicity of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae) aqueous extract (leaves, petioles and branches) and its performance in a nociceptive response. Hepatotoxicity, psycho-stimulant test and evaluation of enzyme markers for liver damage were also tested. Chromatographic analysis by UPLC-MS demonstrated a series of isomeric monocaffeoylquinic acids, isomers of dicaffeoylquinic acid, flavonol glycosides, and saponins. Phase I and II of nociception were obtained for meloxicam, dexamethasone and aqueous Ilex paraguariensis extract. Ilex paraguariensis extract concentration was negatively correlated (R = –0.887) with alanine aminotransferase (p < 0.05) in acetaminophen-induced hepatotoxicity test, indicating hepatoprotective activity of this extract. Ilex paraguariensis extract also presented analgesic properties equivalent to drugs that already have proven efficacy. Notably, the administration of multiple doses of Ilex paraguariensis extract was considered safe from the therapeutic point of view.

Investigating the effect of the Teucrium polium aqueous extract on the liver of the streptozotocin-induced diabetic rats

Objectives Teucrium polium (TP) has been traditionally used for treatment of the diabetes mellitus, kidney and liver diseases, and inflammations but some studies have reported the hepatotoxicity effects of this plant. Therefore, this study was conducted to investigate the effect of TP aqueous extract on the liver of the diabetic rats. Methods Adult male Wistar rats were randomly divided into five groups: (Control) Normal rats that were gavaged with normal saline (1 mL), (TP100) Normal rats (Non-diabetic) that were gavaged with TP (100 mg/kg), (DM) diabetic model rats, which became diabetic by intraperitoneal injection of streptozotocin (50 mg/kg), (DTP100) diabetic rats that were gavaged with TP (100 mg/kg), and (DTP200) diabetic rats that were gavaged with TP (200 mg/kg). The effects of the aqueous extract on the blood glucose, body weight, the activities of enzyme markers of liver damage (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) were investigated in the serum of the control and treated groups. At the end of study liver histopathology and the total antioxidant activity (TAA) test were evaluated. Finally, obtained data were analyzed by the SPSS software (version 16). Results Results showed that the AST and ALT levels were significantly increased in the diabetic rats (p<0.001). A comparison of 100 mg/kg and 200 mg/kg doses of TP administration in diabetic rats also showed a significant difference (p=0.01), indicating a better performance of 100 mg/kg dose. No significant difference was found between the control group and rats treated by the TP (TP100) (p=0.382). Also, triglyceride (TG) and cholesterol levels were significantly decreased in the treated groups compared to the diabetic untreated group. Conclusions Findings of the study revealed no hepatotoxicity, and the hepatoprotective effects of the TP were proved in the present study.

Cardioprotective Effects of Metformin in Ovariectomized Albino Wistar Rats

The current study used a human-equivalent therapeutic dose of metformin to address cardioprotective properties of the drug in ovariectomized rats. Sixty adult female rats were divided equally into four groups. Animals in Group 1 were sham-operated (n = 15), and rats in Groups 2–4 (n = 45) were ovariectomized. After one month, animals Groups 3 and 4 were treated with E2 (100µg/kg, i.m., every other day, n = 15) and MF, (100 mg/kg/day orally, n = 15), respectively. These treatments continued for one month. Ovariectomized rats (Group 2) showed significant elevation in serum heart enzyme markers. MF-treated animals (Group4) showed a superior response to treatment compared to E2 treated rats (Group 3) in restoring enzyme levels of CK-MB and LDH toward control levels. Compared to Group 2 animals, MF and E2-treated rats showed a significant decrease in serum angiotensin II, cardiac MDA, and NOx levels and a significant increase in cardiac CAT activity and Total antioxidant capacity. Group 2 animals showed dyslipidemia. MF treatment renormalized lipid profile markers, but E2 treatment did not induce a significant effect. Group 2 animals also showed significant elevation in proinflammatory markers. Both MF and E2 treatment significantly decrease levels of TNF-α and IL-6. A focus on cardiac dysfunction markers, dyslipidemia and cardiac oxidative insult allowed the demonstration that MF is superior to E2 for attenuating cardiotoxicity. Further, MF and estradiol are similar in their ability to mitigate inflammation.

Protective effects of Cyathula prostrata leaf extract on olanzapine-induced obese rats

Olanzapine, an atypical antipsychotic drug often induces excessive weight resulting in obesity. The adverse effect hinder adherence to drug regimens and therefore relapse into psychosis. Traditionally in Nigeria, leaf broth from Cyathula prostrata leaf is consumed to achieve weight loss. Rats were first administered 50-200 mg/kg bw CPLE and orlistat (5 mg/kg bw), used as reference. Rats were then administered 8 mg/kg bw of olanzapine one hour after the administration of the CPLE and orlistat, all the administration were done for 28 days. Those with body mass index (BMI) ˃ 0.5 g/cm2 were considered obese. The influence of the extract at varying doses on BMI, lipid profiles, oxidative and enzyme markers in the heart and liver of the obese rats were evaluated. Anthropometric data showed that CPLE significantly (p < 0.05) induced weight loss and attenuated BMI increase when compared to untreated olanzapine-induced obese rats. Biochemical analyses also revealed reduction in the serum level of LDL-c, total cholesterol, triglycerides, lipase and creatine kinase activities in CPLE-treated groups. Concentration of malondialdehyde was decreased, while the activities of antioxidant enzymes as well as that of alkaline phosphatase, alanine and aspartate aminotransferase were increased following administration of CPLE to the obese rats. Findings from this study supported the indigenous use of extracts from C. prostrata leaf in the management of obesity. The study concluded that CPLE can protect against weight gain, obesity, dyslipidaemia, oxidative stress and alteration in the heart and liver function parameters induced by olanzapine co-administration in rats.

Activities of Acetylcholinesterase, Oxidative and Nitrosative Stress Markers in Clarias gariepinus Exposed to ‘Uproot’, a Glyphosate–Based Herbicide

In this study, Clarias gariepinus were exposed to different concentrations (60, 80 and 100 mg/L) of Uproot, a glyphosate-based herbicide and the activities of acetylcholinesterase (AChE), hepatic enzyme markers, oxidative and nitrosative stress markers were determined in serum, gills, liver and brain by using standard assays. Results showed that AChE activity was not significantly inhibited. Activities of ALT, AST and ALP increased (P < 0.05) with increasing exposures. For SOD, elevated (P < 0.05) activities were observed in all tissues at 60 mg/L exposure, but decreased at 80 mg/L and 100 mg/L concentrations. The activity of CAT reduced significantly (P < 0.05) in brain at 100 mg/L exposure. Increased production of NO was observed in gill and brain whereas in serum it is increased. GPx was elevated in gills and reduced in brain and liver. Gills showed lower MDA concentrations. GST was el evated in liver and brain, while total protein reduced (P < 0.05) in serum, gill and liver with increasing concentrations of exposure. The impaired activities of antioxidant enzymes and induction of NO suggest a disruption of normal antioxidant response in Clarias gariepinus exposed to glyphosate, and these activities could be used as biomarkers in aquatic environmental contamination

Phytochemical Screening of Cinnamon Cassia and Its Protective Effects Against Hepatotoxicity Induced By Difenoconazole in Male Albino Rats.

The objective of the present study has focused on the phytochemical analysis of Cinnamon cassia bark for determination of bioactive components, which have been associated with antioxidative stress induced by difenoconazole treatment in hepatic tissue of male albino rats. Ninety rats were assigned randomly to 9 groups, each group comprised of 10 animals. The first group served as control animals were administrated distilled water and the rest served as the experimental groups. Groups II and III animals were orally administrated with difenoconazole at doses of 58.9 and 117.8 mg/kg BW (represent of 1/20 and 1/10 of oral LD 50 , respectively) while the groups IV and V animals were received aqueous extract of cinnamon (AEC) at doses of 200 and 400 mg/kg BW , respectively . In addition groups VI and VII, animals were received AEC prior to 2h of administration with difenoconazole at low dose as well as groups VIII and IX, rats were received with AEC before treatments with high dose of difenoconazole for 28 days. Results of the present study indicated the presence of total phenolic, flavinoids and tannins as the main bioactive components in the AEC. Furthermore, the final body weight and liver index were increased markedly in difenoconazole-treated rats and these parameters values were comparable to control group following co-administration with AEC. However, difenoconazole-treatment induced a significant elevation in the level of (LPO) associated with adepletion of GSH level and an elevation in the activities of serum liver enzyme markers (i.e., AST ,ALT,ALP and GGT) was observed. These results confirmed with histopatlogical findings . In contrast, treatment with AEC in difenoconazole-treated rats elevated the level of endogenous hepatic antioxidant system (SOD, CAT and GSH) along with reducing the activities of serum liver enzymes. However, the hepatic protective property of AEC was further confirmed by histopathological findings. These findings may be attributed to the presence of total phenolic , flavoniods and tannins , which have anti-oxidative effect against oxidative injury- induced by tested fungicide.

Possibilities for correcting hepatotoxic reactions during therapy in patients with COVID-19 (case report)

In 2020, a pandemic of the new coronavirus infection (COVID-19) began. Treatment of this infection is limited by the lack of effective etiological treatment, which requires the selection of empirical and symptomatic therapy. The obtained some effectiveness of the use of antimalarial drugs, antiretroviral drugs in combination with antibacterial therapy made it possible to recommend it for use in the treatment regimen for patients with COVID-19. However, these drugs provoke the development of undesirable side reactions that require correction to continue treatment. Considering the need to use complex therapy in the treatment of patients with COVID-19 and the direct effect of the virus on liver cells, the likelihood of developing hepatotoxicity is quite high. The described cases of liver damage are characterized by impaired functional activity, an increase in the level of liver function tests, the development of small-drop fatty infiltration and a mild inflammatory reaction in the liver lobules. The development of these complications requires the hepatoprotective drugs, which increase the liver’s resistance to the damaging effects of various pathogens and help restore the functional activity of hepatocytes. According to the conducted studies, hepatotropic drug inosine+ + meglumine + methionine + nicotinamide + succinic acid and reamberin contribute to the normalization of lipid metabolism, a decrease in the level of enzyme markers of liver damage. The article presents the complex treatment with lopinavir + ritonavir. Thanks to hepatoprotective therapy, a week later, a decrease in ALT, alpha-amylase, blood counts to normal values was achieved.

Pre-treatment effects against the diclofenac-induced toxicity by the aqueous leaf extract of Madhuca longifolia on female Wistar albino rats for 10 and 15 days

Diclofenac is used to treat rheumatism disorders, which are associated with the damages of renal, gastric and hepatic organs. Diclofenac is a pharmaceutical drug that is known to induce toxicity on its overdosage and long-term usage. Madhuca longifolia is known to have antioxidant, anti-inflammatory and anti-ulcer activity. It is an evergreen tree that is reported to have many ethnomedicinal uses. The other properties of Madhuca longifolia include anti-diabetic, analgesic and anti-microbial activities. Our study aims to evaluate the pre-treatment activity against the diclofenac-induced toxicity by the Madhuca longifolia aqueous leaf extract in Wistar albino rats for 10 and 15 days. Rats were divided as Group-I: Normal control, Group-II: Diclofenac on the last two days, Group-III and group-IIIa: Diclofenac + Aqueous Leaf Extract of Madhuca longifolia, Group-IV and group-IVb: Diclofenac + Silymarin, Group -V and group-Va: Aqueous Madhuca longifolia leaf extract. After the sacrifice, the rats were studied for antioxidant assay, renal enzyme markers, liver enzyme markers, and histopathological analysis of the kidney, stomach, intestine, and liver. As a result, we could identify that Madhuca longifolia has reduced the toxic changes in rats caused by diclofenac.

Pathophysiology of high fat diet induced obesity: impact of probiotic banana juice on obesity associated complications and hepatosteatosis

The high fat diet alters intestinal microbiota due to increased intestinal permeability and susceptibility to microbial antigens leads to metabolic endotoxemia. But probiotic juices reported for various health benefits. In this background we hypothesized that pectinase treated probiotic banana juice has diverse effects on HFD induced obesity and non-alcoholic steatohepatitis. 20 weeks fed HFD successfully induced obesity and its associated complications in experimental rats. The supplementation of probiotic banana juice for 5 months at a dose of 5 mL/kg bw/day resulted significant decrease (p < 0.05) in body weight (380 ± 0.34), total fat (72 ± 0.8), fat percentage (17 ± 0.07) and fat free mass (165 ± 0.02). Reduction (p < 0.05) in insulin resistance (5.20 ± 0.03), lipid profile (TC 120 ± 0.05; TG 160 ± 0.24; HDL 38 ± 0.03), liver lipid peroxidation (0.7 ± 0.01), hepatic enzyme markers (AST 82 ± 0.06; ALT 78 ± 0.34; ALP 42 ± 0.22), and hepatic steatosis by increasing liver antioxidant potential (CAT 1.4 ± 0.30; GSH 1.04 ± 0.04; SOD 0.82 ± 0.22) with normal hepatic triglycerides (15 ± 0.02) and glycogen (0.022 ± 0.15) contents and also showed normal liver size, less accumulation of lipid droplets with only a few congestion. It is concluded that the increased intestinal S. cerevisiae yeast can switch anti-obesity, antidiabetic, antioxidative stress, antioxidant and anti-hepatosteatosis effect. This study results will have significant implications for treatment of NAFLD.