Investigation of homocysteine, D-dimer and platelet count levels as potential predictors of thrombosis risk in COVID-19 patients.

Thrombosis plays an important role in induction of Coronavirus disease 19 (COVID-19) complications including heart attack and stroke. Reliable biomarkers are needed to predict thrombosis risk for better management and improve patient outcomes. This study aimed to investigate the relationship between homocysteine, a thrombosis-related biomarker, and other thrombosis-related parameters, such as D-dimer and platelet count with disease outcome in COVID-19 patients. This case-control study including 50 intensive care unit hospitalized patients with Covid-19 with a positive RT-PCR test for SARS-CoV-2 infection and 50 healthy individuals as a control group was conducted. Both groups were matched for age and body mass index (BMI) and had no history of underlying diseases such as cardiovascular, liver, kidney or smoking. Blood samples were collected from both groups to measure serum homocysteine, platelet count and D-dimer levels. Data were analyzed using GraphPad Prism version 8.3 software. The study found no statistically significant difference in homocysteine levels between COVID-19 patients and the control group. However, D-dimer levels were significantly higher in the patient group. Platelet count analysis revealed a significant difference between patients who died and those who were discharged from the hospital (P < 0.05). Despite previous studies suggesting a link between homocysteine and thrombosis, this study found no significant difference in homocysteine levels between COVID-19 patients and the control group. The significantly elevated D-dimer levels in the death group patient suggest that D-dimer and thrombocytopenia may be more reliable predictors of thrombosis and worse outcome in COVID-19 patients without underlying diseases.

Role of cineole in alleviation of acute kidney injury and renal function recovery following gentamicin administration in rats.

Objectives: Gentamicin leads to kidney failure by producing free radicals and inflammation in renal tissue. Cineole as a terpenoid has antioxidant properties. Antioxidants can play an effective role in preserving the oxidant-antioxidant balance. Hence, this study investigated the effects of cineole on acute kidney injury (AKI) and renal function recovery following gentamicin administration in rats. Materials and Methods: 36 male Wistar rats were randomly divided into 6 equal groups; healthy control, gentamicin, DMSO carriers, cineole 50, cineole 100, and vitamin E. After 12 days of treatment, the animals were anesthetized with ketamine and xylazine. Serum and kidney samples were taken for biochemical and gene expression experiments. Results: Cineole 50 and 100 groups increased the levels of serum glutathione (GSH) (<0.05), kidney and serum glutathione peroxidase (GPX) (<0.001), kidney catalase (CAT) (<0.001), serum nitric oxide (NO) (<0.001), and the GPX gene (<0.05) compared with the gentamicin group. These treatment groups had decreased levels of kidney malondialdehyde (MDA) (<0.001), serum creatinine (<0.001), urine protein, and the Interleukin 6 (IL-6) gene (<0.05) compared with the gentamicin group. Cineole 50 increased the serum MDA (<0.001), urea, and CAT gene (>0.05) and decreased the kidney GSH (<0.05) and the tumor necrosis factor-alpha (TNF-α) gene (<0.05). Cineole 100 increased the kidney GSH (<0.05) and decreased the serum MDA (<0.001), urea, CAT gene (>0.05), and TNF-α gene (>0.05) compared with the gentamicin group. Improvement in histological alterations was displayed in cineole groups compared with the gentamicin group. Conclusion: Cineole can reduce kidney damage caused by nephrotoxicity following gentamicin consumption through its antioxidant and anti-inflammatory properties.

The Effect of Thyme Essential Oil on Liver Injuries Caused by Renal Ischemia-Reperfusion in Rats.

Liver damage occurs following renal ischemia-reperfusion (RIR) that can cause inflammation and inflammatory cytokines activated after kidney injury. In this study, thyme essential oil (TE) with antioxidant and anti-inflammatory properties was used to reduce liver damage induced by renal IR. 32 male rats were randomly divided into 4 equal groups: (1) control, (2) RIR, (3) RIR+TE, and (4) TE. Rats received TE as a pretreatment at a dose of 0.5 ml/kg for one week. Then, under anesthesia for 45 minutes for ischemia, the kidneys of the animals were closed with clamps, and reperfusion was performed for 24 hours. Animal serum was isolated to evaluate alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) parameters. The liver of rats was examined for the measurement of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), and expression of genes such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3. ALP, AST, ALT, MDA, NO, IL-6, TNF-α, and caspase-3 increased significantly in the RIR group compared to the control group (p < 0.05). GSH, GPX, and CAT decreased significantly in the RIR group compared to the control group (p < 0.05). TE caused a decrease in ALP, AST, ALT, MDA, NO, IL-6, and TNF-α compared to the RIR group and caused an increase in the amount of GSH, GPX, and CAT in the RIR group (p < 0.05). This study showed that TE has antioxidant and anti-inflammatory properties that reduce liver damage induced by RIR.

Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression.

BACKGROUND: Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin's dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. METHOD: Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. RESULTS: The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. CONCLUSION: Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity.

BACKGROUND: Thrombosis plays an important role in the Coronavrus Disease 2019 (COVID-19) infection-related complications such as acute respiratory distress syndrome and myocardial infarction. Multiple factors such as oxygen demand injuries, endothelial cells injury related to infection, and plaque formation. MAIN BODY: Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases. Platelets contain multiple receptors that interact with specific ligands. Pathogen's receptors such as Toll-like receptors (TLRs), NOD-like receptor, C-type lectin receptor family, glycoprotein (GP) such as GPαIIbß3 and GPIbα which allow pathogens to interact with platelets. Platelet TLRs and NOD2 are involved in platelet activation and thrombosis. Accordingly, TLRs are critical receptors that could recognize various endogenous damage-associated molecular patterns and exogenous pathogen-associated molecular patterns (PAMPs). TLRs are considered as important components in the activation of innate immunity response against pathogenic and non-pathogenic components like damaged tissues. TLRs-1,-2,-4,-6,-7 expression on or within platelets has been reported previously. Various PAMPs were indicated to be capable of binding to platelet-TLRs and inducing both the activation and promotion of downstream proinflammatory signaling cascade. CONCLUSION: It is possible that the increased TLRs expression and TLR-mediated platelets activation during COVID-19 may enhance vascular and coronary thrombosis. It may be hypothesized using TLRs antagonist and monoclonal antibody against P-selectin, as the marker of leukocyte recruitment and platelet activation, besides viral therapy provide therapeutic advances in fighting against the thrombosis related complications in COVID-19.

Coagulation abnormalities in SARS-CoV-2 infection: overexpression tissue factor.

Among the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1ß, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.