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.

Medicinal plants with hepatoprotective potentials against carbon tetrachloride-induced toxicity: a review

Background Carbon tetrachloride (CCl4) is a well-characterized hepatotoxic agent. With rising cases of liver diseases, the identification, assessment, and development of hepatoprotective agents from plants source has become imperative. Main body With arrays of literature on plants with hepatoprotective potentials, this review sourced published literatures between 1998 and 2020 and systematically highlighted about 92 medicinal plants that have been reported to protect against CCl4-induced liver injury in animal models. The results show that herbal plants provide protection for the liver against CCl4 by downregulation of the liver marker enzymes and activation of antioxidant capacity of the liver cells with the restoration of liver architecture. We also provided the traditional and accompanying pharmacological uses of the plants. A variety of phytochemicals mostly flavonoids and polyphenols compounds were suggested to offer protection against liver injuries. Conclusion It can be concluded that there are a variety of phytochemicals in plant products with hepatoprotective activity against CCl4-induced toxicity in animal models.

Effective Antioxidant activity of Phytic acid Prevents Isoproterenol-Induced Myocardial Infarction in Albino wistar Rats

This study aimed to evaluate the preventive effect of phytic acid on cardiac markers, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, and plasma iron binding capacity in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days showed a significant increase in the degrees of cardiac troponin T (cTnT), intensity of the bands of lactate dehydrogenase (LDH)-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart. ISO-induced rats showed a significant increase in blood glucose, serum uric acid, serum iron and a decrease in the levels of total proteins, A/G ratio and iron binding capacity. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, and other biochemical parameters. Thus, phytic acid possess cardioprotective effect in ISO-induced oxidative stress in rats.

DOSE-DEPENDENT PROTECTIVE FEATURES OF LOBOPHORA VARIEGATA METHANOLIC EXTRACT (LVME) IN N-NITROSODIETHYLAMINE INDUCED EXPERIMENTAL HEPATOCARCINOGENESIS IN RATS

Objective: This study explores the anti-cancer property of Lobophora variegata, also an effective dose to treat hepatocarcinoma in Male Albino Wistar rats in N-nitrosodiethylamine induced hepatocarcinoma paradigm and its possible mechanism of action. Methods: In this study, rats were segregated into five groups; group-1 (control), group-2 treated with 0.01% NDEA through drinking water for 15 w, group-3 NDEA+treated with Lobophora variegata methanolic extract (LVME) (100 mg/kg b.w.), group-4 NDEA+treated with (LVME) (200 mg/kg b.w.) and group-5 NDEA+treated with (LVME) (400 mg/kg b.w.). Results: After the experimental period, functional and morphological changes in the liver were observed both macro and microscopically, the activities of liver marker enzymes, alkaline phosphatase (ALP), aspartate and alanine transaminases (AST and ALT) were analyzed. Administration of LVME as 200 mg/kg b.w. (to NDEA treated rats) significantly (i) reduced the preneoplastic lesions alleviated lipid peroxidation through scavenging free radicals, (ii) enhanced antioxidant status and reverted liver/disease marker enzymes plausibly by modulating xenobiotics metabolizing enzymes (XMEs) and by exhibiting antiproliferative and cytoprotective effects. Conclusion: LVME doses higher than 200 mg/kg b.w. are not effective in quenching the free radicals and restoring the liver functions as saturation level could have been reached; also, doses lower than 200 mg/kg b.w. could not be effective as they are below the optimum dose required to exhibit the pharmacological effects.

Gonadal rejuvenation of mice by GDF11

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), has been shown to have rejuvenation and anti-aging properties, but little information is available regarding the role of GDF11 in reproductive system to date. In this study, we first confirmed the bioavailability of recombinant GDF11 (rGDF11) by oral delivery in mice. We also showed that dietary intake of rGDF11 had little influence on body and gonadal (ovary/testis) weights of recipient mice, indicating their general condition and physiology were not affected. Based on these findings, we started to test the function of rGDF11 in ovary and testis of mice and to explore the underlying mechanisms. It was found that to some extent, rGDF11 could attenuate the senescence of ovarian and testicular cells, and contribute to the recovery of ovarian and testicular endocrine functions. Moreover, rGDF11 could rescue the diminished ovarian reserve in female mice and enhance the activities of marker enzymes of testicular function (SDH and G6PD) in male mice, suggesting a potential improvement of fertility. Notably, rGDF11 markedly promoted the activities of antioxidant enzymes in the ovary and testis, and remarkably reduced the levels of lipid peroxidation, protein oxidation and ROS in the ovary and testis. Collectively, these results suggest that GDF11 can protect ovarian and testicular functions of aged mice via slowing down the generation of ROS through enhancing activities of antioxidant enzymes.

Beneficial Role of Ginger Powder (Zingiber officinale) against Acephate-induced Reprotoxicity in Adult Male Rats

Aims: The present study was aimed to investigate the protective role of ginger against acephate-induced testicular toxicity in adult rats. Methodology: Rats were allocated into four groups where animals in group I served as controls, while animals in group II, III and group IV were treated as experimental rats. Rats in groups II, III and IV were treated with acephate (50mg/kg body weight), ginger (100mg/kg body weight) and combination of both acephate and ginger, respectively over a period of 60 days. After completion of experimental period sperm count, sperm viability, sperm motility, sperm membrane integrity, testicular steroidogenic marker enzymes (3β-HSD and 17β-HSD, serum testosterone and testicular architecture was performed in both control and experimental rats. Results: Relative weights of reproductive organs, sperm count, sperm viability, sperm motility and sperm membrane integrity were significantly decreased in acephate treated rats over controls. Acephate administration also reduced the circulatory levels of testosterone associated with a significant reduction in the testicular steroidogenic marker enzymes (3β-HSD and 17β-HSD) in rats. The testicular architecture was disrupted in acephate intoxicated rats. In contrast, ginger administration significantly recovered the acephate-induced suppressed selected reproductive parameters with increased circulatory levels of testosterone and restoration of sperm endpoints in as compared to acephate alone treated rats. No significant changes were observed in any of the selected reproductive endpoints in ginger treated rats as compared to controls. Conclusion: The results can be concluded that supplementation of ginger mitigates the negative effects of acephate on male reproductive health via amelioration of testicular setroidogenesis and spermatogenesis and epididymal sperm maturation events in rats.

The role of the macrophage polarization type in the pathogenesis of endometrioid disease

Endometriosis today occupies one of the leading places in the structure of general gynecological pathology. Theories of the onset and progression of this disease are controversial. One of the most widespread theories is the assumption that endometriosis is a disease of macrophages. The question of which the macrophage phenotype, M1 or M2, is the leading one, however, remains controversial. The aim. To determine the type of macrophage polarization (M1/M2) and the quantitative activity of their marker enzymes (iNos/Arg1) in the endometrium and peritoneal fluid in endometrioid disease. Materials and methods. The total number of reproductive age (30.95±6.49) women enrolled in the study was 80. The main group consisted of 50 women with endometrioid disease. The control group included 30 women without signs of endometrioid disease. Women from the main group (n=24) and the control group (n=27) underwent endometrial sampling using an intrauterine Pipelle catheter in the first phase of the menstrual cycle before a surgery. During laparoscopic or laparotomy approaches, peritoneal fluid was taken (in the main group n=24, in the control group n=28). The type of macrophage polarization (M1 or M2) was determined based on the ratio of marker enzymes (Arg1, iNos) activity in each patient using a spectrophotometric method in the endometrium and peritoneal fluid. The polarization to the M1 phenotype was determined at iNos>Arg1, and at Arg1>iNos– the polarization to the M2 phenotype. Results. As a result of the study, it was revealed that in women with endometrioid disease, pelvic adhesions were much more common, 84.0% versus 46.7% in women without it, and especially 3 and 4 degree of severity (P<0.05). When assessing the type of macrophages in the peritoneal fluid, a significantly greater number of the main group women had the M2 phenotype of macrophage polarization compared to the control group (58.3% versus 28.6%, P=0.03). It was the macrophage polarization to the M2 phenotype that influenced the severity of endometrioid disease, especially the 4 degree of severity. The mean values of the iNOS activity in the main group women, both in the peritoneal fluid and in the endometrium, significantly differed from those in the control group patients (by 1.73 and 1.77 times, respectively). Conclusions. Thus, we can conclude that endometriosis is a disease, the development and progression of which is induced by the M2 phenotype of macrophages. Considering the increase in the mean levels of iNOS activity both in the peritoneal fluid and in the endometrium, it can be concluded that iNOS influences the pathogenesis of endometrioid disease.

Hepatoprotective Potential of Tecomella undulata Bark on Paracetamol and CCL4 Induced Hepatotoxicity in Rats: Invitro Analysis

In this study the T. undulata bark was tested for its hepatoprotection against paracetamol (PCM) induced hepatic damage and Carbon tetra chloride (CCl4) induced hepatotoxicity. The Invitro study was performed on HepG2 cell line .The Levels of serum marker enzymes i.e. AST, ALT (aminotransferases), ALP (alkaline phosphatase), GSH (reduced glutathione) and MDA (Malondialdehyde) in 70% Ethanol treated rats were monitored, respectively. The 70% Ethanol extract gave promising results as studied in detail. The Present study showed that the 70 % ethanolic extract of bark of T.undulata apparently revive the physiological integrity of hepatocytes. Thus the present study demonstrated the Hepatoprotective property of Tecomella undulate Bark.

Pharmacodynamics Interaction of Quercetin and Captopril on Doxorubicin Induced Myocardial Toxic Rats

Captopril (CAP), an ACE inhibitor, is widely used in the therapy of cardiovascular disease. Quercetin (QUE), a plant-derived flavonol that exerts cardioprotective activity through its antioxidant mechanism. A combination of CAP and QUE may produce synergistic or antagonistic cardioprotective effects. Therefore, the present study was designed to evaluate the pharmacodynamics interaction of QUE and CAP in Doxorubicin (Dox) induced oxidative myocardial damage in rats. Rats were pretreated with normal saline, QUE (10 mg/kg), and CAP (30 mg/kg) alone and in combination orally for 14 days. On the 14th day of treatment, rats were injected with Dox (10mg/kg single dose i.p) for the induction of myocardial damage. There was a substantial fall and rise in activities of marker enzymes such as CK-MB, LDH, AST, and ALT in serum and elevation of ST-segment, increased QT interval, and HR upon Dox administration. Pretreatment with QUE and CAP alone significantly restored the above parameters. But, the Concomitant pretreatment with QUE and CAP was found to be less significantly restored the Dox-induced alterations. The present study suggests that concomitant pretreatment with CAP and QUE could attenuate cardiovascular protection than that of alone pretreatment. It may be due to the antagonistic effect between the two drugs.

​Impact of Extreme Hot Environmental Temperature Period on Marker Enzymes of Carbohydrate Metabolism in Non-descript Sheep from Arid Tracts of Rajasthan

Background: The present investigation was envisaged to find out the impact of extreme hot environmental temperature period (ETP) on marker enzymes of carbohydrate metabolism in male and female non-descript sheep of various age groups i.e. 4 to 13 months from arid tracts of Rajasthan. Glucose-6-phosphate dehydrogenase (G-6-PDH) and malate dehydrogenase (MDH) marker enzymes of carbohydrate metabolism were considered for study. Methods: During the period October 2016-June 2017 blood samples were collected to harvest sera for spectrophotometric method from 240 healthy animals selected from private slaughter house during moderate and extreme hot environmental temperature periods (ETPs). The mean values of markers attained during moderate ETP were reckoned as the control. It was 10.00 ± 0.10 UL-1 and 42.00±1.00 respectively. Conclusion: The mean value of MDH was significantly (p≤0.05) higher while G-6-PDH significantly (p≤0.05) lowers during extreme hot temperature in comparison to moderate period. Therefore, it could be concluded that variations in enzyme markers were associated with changes in environmental temperatures. Probably ETP were able to produce a profound effect on carbohydrate metabolism in sheep. Therfore it can be suggested that during the period of extreme temperature balanced ration must be provided to the animal along with proper management to decrease the severity of temperature impact.