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Introduction: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19., Methods: This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented., Results: Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity., Conclusions: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: To elucidate the anti- Methicillin resistance Staphylococcus aureus (MRSA) effect of pomegranate alone and in combination with moxifloxacin fluoroquinolone., Methods: A total of five clinical isolates of MRSA (ATCC 43300) were used in the study. Disc diffusion method was used to determine the anti-MRSA effect of pomegranate and/or moxifloxacin by using Mueller-Hinton agar. Minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) of moxifloxacin and pomegranate were calculated, the dynamic picture of the bactericidal effect of pomegranate and/or moxifloxacin was determined. SPSS version 20.00 was used for data analysis., Results: Zone of inhibition (ZOI) of moxifloxacin was 19.67±4.84mm which was not significant compared with pomegranate ZOI 14.59±2.73mm, (P=0.07). The combination of moxifloxacin and pomegranate led to more significant ZOI (26.83±4.91mm) compared with moxifloxacin (P=0.04) and pomegranate alone (P=0.0012). MIC of pomegranate was high (31.62±6.95mg/mL) compared with low MIC of moxifloxacin (2.70±0.63 mg/mL), (P<0.0001), while MIC of the combination was low (1.22±0.85mg/mL) compared MIC of moxifloxacin, (P=0.012). FIC of pomegranate was 0.038 and FIC of moxifloxacin was 0.45, therefore sFIC index was 0.488, equal to the synergistic effect. The kill rates of combination were higher than those of pomegranate or moxifloxacin, against MRSA ATCC 43300., Conclusions: Ellagic acid-rich pomegranate extract alone has significant antibacterial activity and synergizes the bactericidal effect of moxifloxacin against MRSA.

Covid-19 is associated with different neurological manifestations. About one third of Covid-19 patients have some neurological disorders as paresthesia, headache, cold extremities and disturbances of consciousness, which are more evident in severely affected patients. These neurological manifestations may coexist or precede the onset of respiratory manifestations by about 2-3 weeks. Acute ischaemic stroke (AIS) and associated brain damage may develop due to acute respiratory distress syndrome (ARDS) induced-hypoxia. Prolonged hypoxia in late-stage Covid-19 leads to vasodilatation, intracranial hypertension, brain oedema, and AIS. In view of substantial evidence, this perspective explores the potentially direct or indirect effect of SARS-CoV-2 on the Central Nervous System of patients with COVID-19 pneumonia. The AIS is the end of most Covid-19-induced neurological complications. Covid-19 can lead to various neurological manifestations due to involvement of CNS directly through olfactory neurons or indirectly through induction of cytokine storm.

Coronavirus disease 2019 (Covid-19), leads to global calamitous effects. Covid-19 is caused by a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 is associated with development of hyper-inflammation and/or cytokine storm that together with high viral load trigger tissue damage and multi-organ failures (MOF). Colchicine (CN) is a lipophilic tricyclic alkaloid used for treatment of gout since ancient time. In Covid-19 era, CN is repurposed for treatment of SARS-CoV-2 infection depending on its anti-inflammatory and broad-spectrum antiviral effects. Therefore, a recent clinical trial recommends use of CN in treating Covid-19 patients. It has been confirmed that inhibition of neutrophil chemotaxis, lysosomal degranulation, and release of pro-inflammatory cytokines is the main mechanism by which CN produces anti-inflammatory effects. CN attenuates generation of free radicals and reactive oxygen species (ROS) with consequent inhibition release of pro-inflammatory cytokines. Different studies illustrate that microtubule network is necessary and important for replication of different viruses including SARS-CoV-2 since; intracellular transport of viral particles is mediated through cytosolic microtubules. Therefore, CN therapy is effective in the management of Covid-19 patients when timely administrated through reduction of tissue damage and hyper-inflammations. Thus, the anti-inflammatory, antiviral, and immunomodulatory properties of CN might be the potential mechanisms of CN therapy against Covid-19. The review concludes that CN is a potent anti-inflammatory agent for the management of Covid-19; it inhibits SARS-CoV-2-induced-acute lung injury(ALI) due to its anti-inflammatory and anti-viral effects.

Covid-19 is caused by a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 binds angiotensin converting enzyme 2 (ACE2), which is greatly expressed in different tissues including lung alveolar type II cells. Infection with SARS-CoV-2 triggers acute host immune response, inflammatory reactions and cytokine storm leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different studies reported the pleiotropic effects of statins such as the anti-inflammatory and immune-modulatory effects via modulation of antigen presentation and adhesion of inflammatory molecules since; statins have potential anti-oxidant and redox balance effects that improve endothelial dysfunction and cardiovascular integrity. Objective of the present study is to verify the beneficial and harmful effects of statins in Covid-19. Statins upregulates ACE2 receptors and attenuates the down-regulation effect of SARS-CoV-2 on the ACE2 receptors. Consequently, reduction of ACE2 receptors augment the deleterious effect of angiotensin II (AngII) which causes vasoconstriction and initiation of ALI. On the other hand, statins therapy may increase risk of viral infections such as SARS-CoV-2 via lowering of low density lipoprotein (LDL) since; circulating LDL adhere and inactivates SARS-CoV-2. Statin therapy improves the outcomes of Covid-19 pneumonia through anti-inflammatory, immune-modulation, and in vitro anti-SARS-CoV-2 effects. The antiplatelet and antithrombotic effects may reduce Covid-19 induced-coagulopathy and progression of ARDS.

Background: Acute ischemic stroke (AIS) leads to neuronal and endothelial damage that activate the release of proinflammatory mediators such as lipoprotein-associated phospholipase A2 (Lp-PLA2), which lead to the development of brain edema injury. Most of statins produce differential effects on Lp-PLA2 activity and mass with a comparable reduction in low-density lipoprotein (LDL) serum levels., Aims: The aim of this study is to evaluate the differential effect of different statins on the mass of level of Lp-PLA2 in patients with AIS., Methods: A total of 69 patients with AIS aged 40-70 years compared with matched 39 healthy controls were involved in this case-control study. The AIS patients were divided according to the statins therapy into 39 patients on statins therapy (statins on), and 30 patients were not on the statins therapy (statins off). Anthropometric variables including weight, height, body mass index (BMI), and blood pressure profile were estimated. Besides, biochemical variables including lipid profile[total cholesterol (TC), triglyceride (TG), LDL, very low-density lipoprotein (VLDL), high-density lipoprotein (HDL)], Lp-PLA2 mass levels, high-sensitive C-reactive protein (Hs-CRP) were estimated., Results: Patients with AIS had high Lp-PLA2 mass levels (P < 0.01) that positively correlated with high Hs-CRP, blood pressure, BMI, TC, TG, VLDL, LDL, and negatively correlated with HDL as compared with healthy controls. As well, statins on patients had lower Lp-PLA2 mass levels (9.82 ± 3.19 IU/mL) compared with statins off patients (16.55 ± 4.72 IU/mL), (P = 0.0001). Regarding the gender differences in the Lp-PLA2 mass level, it was higher in men patients with AIS compared with comparable females (P = 0.03)., Conclusions: Lp-PLA2 mass level was higher in patients with AIS and linked with underlying poor cardio-metabolic disorders. Therefore, the Lp-PLA2 mass level is observed to be a surrogate biomarker of AIS mainly in patients with poor cardio-metabolic disorders. Statin therapy improves the Lp-PLA2 mass level and the poor cardio-metabolic profile in patients with AIS., Competing Interests: None

Objective: To evaluate the nephroprotective effect of lycopene (LPN) in acute kidney injury (AKI) regarding the oxidative stress (OS)., Materials and Methods: Thirty Sprague Dawley male rats were divided into three groups - control group: rats treated with distilled water (orally) for 10 days ( n = 10); AKI group: rats treated with distilled water and diclofenac (intraperitoneal) for 10 days ( n = 10); treated group: rats treated with LPN (orally) and diclofenac for 10 days ( n = 10). Body mass index (BMI) and estimated glomerular filtration rate (eGFR) were measured. Blood urea, serum creatinine (CreSerum), serum malondialdehyde (MDA), superoxide dismutase (SOD), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecules (KIM-1) were measured in the all groups on the 11 th day of the experiment., Results: Diclofenac-induced AKI led to significant elevations of BMI, CreSerum, and blood urea compared with control ( P < 0.05). In AKI model, eGFR was reduced to 11.69 ± 2.64 ml/min/1.73 compared with control group (15.88 ± 3.75 ml/min/1.73, P = 0.03). NGAL, MDA, and KIM-1 were elevated in AKI compared with control ( P < 0.001). Pretreatment with LPN led to the reduction of blood urea and CreSerum as compared with AKI ( P < 0.001). Similarly, eGFR was increased significantly to 14.81 ± 3.21 ml/min/1.73 compared with 11.69 ± 2.64 ml/min/1.73 in AKI ( P = 0.02). Serum levels of NGAL, KIM-1, and MDA were reduced significantly in the LPN group as compared with AKI ( P = 0.001), while the SOD serum level was increased to 33. 86 ± 8.61 pg/ml as compared to 22.78 ± 7.56 pg/ml in AKI ( P = 0.006). As well, LPN reduced MDA/SOD ratio as compared with AKI ( P = 0.00001)., Conclusion: The finding of this study illustrated that LPN is an effective natural antioxidant that attenuates and prevents AKI through modulation of OS and lipid peroxidation. As well, LPN might be of great value in the prevention of nephrotoxicity that induced by nephrotoxic agents like diclofenac., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 International Journal of Critical Illness and Injury Science.)

Orexin is a neuropeptide secreted from lateral hypothalamus and pre-frontal cortex concerned in the wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words during the search. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of monoaminergic system, which affect cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotropin and corticosteroid secretions via activation of central corticotropin-releasing hormone. Cerebrospinal fluid (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin serum levels are reduced Parkinson disease, Alzheimer dementia, Huntington's disease, amyotrphic lateral sclerosis, and multiple sclerosis. Orexin antagonist leads to significant reduction of sympathetic over-activity during withdrawal syndrome. As well, orexin antagonist improves sleep pattern. Orexinergic system is involved in the different psychiatric and neurological disorders; therefore, targeting of this system could be possible novel pathway in the management of these disorders. In addition, measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Brain Circulation.)

Prolactin is a polypeptide hormone secreted from the anterior part of the pituitary gland which was implicated as a diabetogenic factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, the aim of the present study was to evaluate prolactin serum levels in patients with T2DM regarding the effect of diabetic pharmacotherapy. Eighty patients with T2DM compared with 25 male healthy controls were recruited and divided into four groups: Group I - 29 patients with T2DM treated with metformin, Group II - 30 patients with T2DM treated with glyburide, Group III - 21 patients with T2DM treated with glyburide plus metformin, and Group IV - 25 control male healthy patients. Prolactin serum levels were high in patients with T2DM compared with controls ( P < 0.01). Prolactin serum levels were higher in glyburide-treated patients compared with metformin-treated patients ( P < 0.01). This study concludes that high prolactin levels in patients with T2DM are linked with diabetic complications and regarded as a beneficial phenomena to overcome IR and diabetic complications. Metformin but not glyburide reduced prolactin levels due to the improvement of insulin resistance., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Advanced Pharmaceutical Technology & Research.)

Statins are hydroxymethylglutaryl-coenzyme A reductase inhibitors inhibit denovo cholesterol synthesis leading to reduction of serum cholesterol and low density lipoprotein as well as elevation of high density lipoprotein level. Statins are used in the treatment of dyslipidaemia, prevention of major cardiovascular events and complications. The potential role of statins in the induction of peripheral neuropathy has not been verified as most of statins induced-peripheral neuropathy had been reported as case reports. Also, statins therapy leads to noteworthy reduction of Coenzyme Q10, causing impairment of neuronal energy. The incidence of polyneuropathy was high with atorvastatin (65%) which is lipophilic, and relatively less with fluvastatin (54%) which is hydrophilic. Long-term statins therapy, mainly with atorvastatin and simvastatin, is linked with thedevelopment of peripheral neuropathy.

Objective: To evaluate the nephro-protective effects of berberine and/or pentoxifylline on the reduction of diclofenac-induced acute kidney injury in rats., Methods: The experimental study was conducted at the Department of Pharmacology, College of Medicine, Mustansiriya University, Baghdad, Iraq, from February to April, 2018, and comprised fifty male Sprague-Dawley rats aged 3-4 months and weighing 250-400 grams each. They were divided into five equal groups and were treated for 12 days. Group 1 rats were treated with distilled water plus normal saline, Group 2 with distilled water plus diclofenac, Group 3 with berberine plus diclofenac, Group 4 with pentoxifylline plus diclofenac, and Group 5 rats were treated with berberine, pentoxifylline and diclofenac. Blood urea, creatinine, Neutrophil Gelatinase Associated Lipocalin (NGAL), kidney injury molecules (KIM-1) and cystatin-C were used to measure the severity of AKI., Results: Diclofenac led to significant AKI by significant elevation of blood urea, serum creatinine level, KIM-1, NGAL. Treatment with berberine showed no significant effect on all biomarkers level compared to diclofenac group except on serum KIM-1 level which was also seen in pentoxifylline group. Whereas, combination of berberine and pentoxifylline led to more significant effect in reduction of all renal biomarkers., Conclusions: Combination of berberine with pentoxifylline led to more significant reno-protective than either berberine or pentoxifylline when used alone on diclofenac induced-AKI.

Objective: To assess the reno-protective effect of berberine on diclofenac-induced acute kidney injury in rats., Methods: The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March 2018, and comprised Sprague Dawley male rats which were divided into 3 equal groups. Group1 rats were treated with distilled water plus normal saline for 14 days, Group2 rats were treated with distilled water plus diclofenac for 14 days and Group3 rats were treated with berberine plus diclofenac for 14 days. Parameters measured were blood urea, serum creatinine, serum malondialdehyde, superoxide dismutase, glutathione reductase, neutrophil gelatinase associated lipocalin, kidney injury molecules-1, Interleukin-18and cystatin-c. Anthropometric measurements and estimated glomerular filtration rate were also noted. SPSS 20 was used for data analysis., Results: Of the 30 rats, the three groups had 10(33.3%) each. Berberine reduced blood urea, serum creatinine, malondialdehyde, neutrophil gelatinase associated lipocalin, kidney injury molecules-1 and Interleukin-18 significantly compared to diclofenac-induced acute kidney injury (p<0.01 each). Berberine improved anti-oxidant capacity through significant elevation of superoxide dismutase and glutathione reductase sera levels (p<0.01 each)., Conclusions: Berberine was found to be an effective agent in the attenuation of diclofenac-induced acute kidney injury through the modulation of pro-inflammatory and oxidative stress biomarkers.

Nephrotoxicity is defining as rapid deterioration in the kidney function due to toxic effect of medications and chemicals. There are various forms, and some drugs may affect renal function in more than one way. Nephrotoxins are substances displaying nephrotoxicity. Different mechanisms lead to nephrotoxicity, including renal tubular toxicity, inflammation, glomerular damage, crystal nephropathy, and thrombotic microangiopathy. The traditional markers of nephrotoxicity and renal dysfunction are blood urea and serum creatinine which are regarded as low sensitive in the detection of early renal damage. Thus, the detection of the initial renal injures required new biomarkers which are more sensitive and highly specific that gives an insight into the site of underlying renal damage. Kidney injury molecule-1, Cystatin C, and neutrophil gelatinase-associated lipocalin sera levels are more sensitive than blood urea and serum creatinine in the detection of acute kidney injury during nephrotoxicity., Competing Interests: There are no conflicts of interest.

Objective: To evaluate the renoprotective effects of berberine and/or pentoxifylline in reduction of diclofenac-induced acute kidney injury (AKI) in rats., Material and Methods: Fifty male Sprague-Dawley rats were allocated into five groups, Group 1: Rats treated with distilled water plus normal saline for 12 days. Group 2: Rats treated with distilled water plus diclofenac for 12 days. Group 3: Rats treated with berberine plus diclofenac for 12 days. Group 4: Rats treated with pentoxifylline plus diclofenac for 12 days. Group 5: Rats treated with berberine + pentoxifylline plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecules (KIM-1), and cystatin-c were used to measure the severity of AKI., Results: Diclofenac led to significant AKI by significant elevation of blood urea, serum creatinine, KIM-1, and NGAL. Treatment with berberine showed no significant effect on all biomarkers level compared to diclofenac group except on serum KIM-1 level which also seen in the pentoxifylline group whereas combination of berberine and pentoxifylline led to more significant effect in the reduction of all renal biomarkers., Conclusion: Combination of berberine with pentoxifylline illustrated a synergistic effect in attenuation of diclofenac-induced AKI., Competing Interests: There are no conflicts of interest.

Sulfonylurea (SUR) agents are the second and most used oral hypoglycemic drugs after metformin and they still as an imperative tool for most favorable of glucose control. SURs are used mainly in the management of Type 2 diabetes mellitus since; they are effective in the glycemic control and reduction of microvascular complications. First-generation SUR represents 3% of used oral hypoglycemic agents while second and third generations are used in about 25% in patients with Type 2 diabetes mellitus. Upregulation of SUR1 receptor has been observed after stroke and traumatic brain injury, therefore, SUR such as glibenclamide inhibits brain edema and astrocyte swelling following brain insults. SUR drugs mainly glibenclamide is effective at a low dose in the management of cerebral stroke and could be a contestant with corticosteroid in controlling brain edema., Competing Interests: There are no conflicts of interest.

Primary hypothyroidism is associated with oxidative stress and insufficient antioxidant capacity. This study was conducted to evaluate the effects of levothyroxine replacement therapy on paraoxonase 1 (PON-1) serum levels in a patients with primary hypothyroidism. Thirty-one patients with primary hypothyroidism compared to 20 healthy controls were recruited from. A venous blood sample were taken after an overnight fasting for biochemical parameters, before and after starting levothyroxine therapy (100 μ g/day) for 3 months duration. The biochemical variables were PON-1 serum levels, lipid profiles, triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone (TSH) serum levels. Levothyroxine replacement therapy leads to a significant amelioration of thyroid functions, lipid profile, cardiometabolic measures P < 0.05 in patients with primary hypothyroidism. Levothyroxine leads to significant elevation in PON-1 serum levels from 188.42 ± 19.81 (U/mL) to 361.23 ± 33.62 (U/mL) P < 0.0001. This study concluded that levothyroxine replacement therapy significantly increases PON-1 serum levels in patients with primary hypothyroidism and attenuating hypothyroidism-induced oxidative stress., Competing Interests: There are no conflicts of interest.