Ameliorative effects of glycine on cobalt chloride-induced hepato-renal toxicity in rats.

BACKGROUND: The important roles of liver and kidney in the elimination of injurious chemicals make them highly susceptible to the noxious activities of various toxicants including cobalt chloride (CoCl2 ). This study was designed to investigate the role of glycine in the mitigation of hepato-renal toxicities associated with CoCl2 exposure. METHODS: Forty-two (42) male rats were grouped as Control; (CoCl2 ; 300 ppm); CoCl2 + Glycine (50 mg/kg); CoCl2 + Glycine (100 mg/kg); Glycine (50 mg/kg); and Glycine (100 mg/kg). The markers of hepatic and renal damage, oxidative stress, the antioxidant defense system, histopathology, and immunohistochemical localization of neutrophil gelatinase associated lipocalin (NGAL) and renal podocin were evaluated. RESULTS: Glycine significantly reduced the markers of oxidative stress (malondialdehyde content and H2 O2 generation), liver function tests (ALT, AST, and ALP), markers of renal function (creatinine and BUN), and decreased the expression of neutrophil gelatinase-associated lipocalin (NGAL) and podocin compared with rats exposed to CoCl2 toxicity without glycine treatment. Histopathology lesions including patchy tubular epithelial necrosis, tubular epithelial degeneration and periglomerular inflammation in renal tissues, and severe portal hepatocellular necrosis, inflammation, and duct hyperplasia were observed in hepatic tissues of rats exposed to CoCl2 toxicity, but were mild to absent in glycine-treated rats. CONCLUSION: The results of this study clearly demonstrate protective effects of glycine against CoCl2 -induced tissue injuries and derangement of physiological activities of the hepatic and renal systems in rats. The protective effects are mediated via augmentation of total antioxidant capacity and upregulation of NGAL and podocin expression.

Supplementation of antihypertensive drug regimen with vitamin E ameliorates alterations of primary haemodynamic parameters and total antioxidant capacity in ovariectomised rats.

OBJECTIVES: Ovariectomy induces heightened response to vasoconstrictors, alters vasorelaxation and consequently causes hypertension due to increased oxidative stress in rats. METHODS: This study evaluated the ameliorative effects of ramipril and vitamin E, on primary haemodynamic parameters and cardiac antioxidant defence status, in ovariectomised rats using 64 adult female rats of the Wistar strain randomly divided as follows: Control (sham); Ovariectomised (OVX); OVX plus Ramipril; OVX plus vitamin E; and OVX plus Ramipril plus vitamin E. RESULTS: The plasma level of oestrogen was significantly lower (p<0.05), in the ovariectomised rats compared with the sham. The systolic, diastolic and mean arterial blood pressure of ovariectomised rats increased significantly (p<0.05), but the alteration was significantly reduced by the administration of ramipril alone or in combination with vitamin E. Significant decrease (p<0.05) was observed in the serum level of nitric oxide in OVX group compared with Sham. Also, analysed markers of oxidative stress: Malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generated decreased significantly (p<0.05), but systemic antioxidants: reduced glutathione (GSH) contents; glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities increased significantly (p<0.05) in the ovariectomised rats treated with ramipril and vitamin E compared with untreated ovariectomised rats. The study concludes that alteration, in the primary haemodynamic parameters, associated with ovariectomy in rats is potently ameliorated by co-administration of the antihypertensive drug ramipril and vitamin E. CONCLUSIONS: The supplementation of antihypertensive regimen with antioxidants such as vitamin E in the treatment of hypertension is therefore justifiable especially in ovariectomised or hypogonadal patients.

Naringin administration mitigates oxidative stress, anemia, and hypertension in lead acetate-induced cardio-renal dysfunction in cockerel chicks.

Lead is one of the major pollutants that is harmful to both animals and humans. It is found in every aspect of the environment such as the air, water, and soil. This pollutant affects both wild and domestic birds. Naringin has an active principle called flavonoid that has been found to have medicinal properties, mostly because of its antioxidant and metal chelating properties. This study was carried out to investigate the protective effect of naringin as an antioxidant against lead-induced anemia, cardio and nephrotoxicity, and hypertension. This study also aimed at elucidating the use of naringin as a heavy metal binder in poultry feed. Thirty-six cockerel chicks were used for this study, and randomly grouped into six groups per group; group A served as the control, group B received Pb-only (300 ppm), group C (Pb and naringin; 80 mg/kg), group D (Pb and naringin; 160 mg/kg), group E (naringin 80 mg/kg), and group F (naringin 160 mg/kg), respectively, for 8 weeks. Lead (Pb) was administered via drinking water, while naringin was administered via oral gavage. Lead acetate intoxication precipitated anemia as indicated by significant reductions in the values of PCV, RBC, and Hb concentration in lead-treated chicks when compared with the controls. Also, lead administration induced hypertension together with increased oxidative stress, depletion of the antioxidant defense system, reduced nitric oxide production, and an increase in high blood pressure. Immunohistochemistry indicated high expressions of cardiac troponin, renal angiotensin-converting enzymes, and renal neutrophil gelatinase-associated lipocalin. Treatment with naringin corrected anemia, reduced oxidative stress, improved antioxidant system, reduced high blood pressure, and offered protection against lead acetate-induced cardio-renal dysfunction in cockerel chicks. We recommend that naringin should be incorporated poultry feeds as a metal binder.

Naringin abrogates angiotensin-converting enzyme (ACE) activity and podocin signalling pathway in cobalt chloride-induced nephrotoxicity and hypertension.

PurposeThe persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl2) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl2-induced hypertension and nephrotoxicity.MethodsForty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl2), Group C (300 ppm CoCl2 + 80 mg/kg NAR), Group D (300 ppm CoCl2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined.ResultsCobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl2.ConclusionTaken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

L-arginine and lisinopril supplementation protects against sodium fluoride-induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity.

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage.

Antioxidant activity enhancement and oxidative damage inhibition by Lagenaria breviflora fruit and Xanthosoma sagittifolium corm in hypertensive Wistar rats.

Cardiovascular diseases are the leading causes of mortality in the world today with hypertension being the major clinical presentation of these diseases. This study assessed the anti-hypertensive effects of Lagenaria breviflora whole fruit and Xanthsoma  sagittifolium corms in experimentally inudced hypertensive Wistar rats. The ability of the plants to ameliorate oxidative damage accompanying hypertension was evaluated using changes in oxidative stress markers as well as monitoring of cardiovascular parameters. Hypertension was induced by intraperitoneal injection of DOCA salt twice weekly and daily inclusion of NaCl (1%) in drinking water. Methanol extracts of L.breviflora or X. sagittifolium was administered to hypertensive rats for 35 days and the outcome was compared to hypertensive rats administred with lisinopril or hydrochlorothiazide and a group of normotensive rats (control). Systolic, diastolic and mean arterial pressures were determined on day 34 and blood sample collected on day 35. The rats were thereafter humanely sacrificed, and organs were harvested. This study showed that the extracts lowered blood pressure, free protein thiols but increased toal protein, gluthathione peroxidase, reduced glutathione, glutathione S-transferase, catalase and nitric oxide in the heart, kidney and liver compared to untreated hypertensive rats. However, malondialdehyde levels and hydrogen peroxide activities were reduced. L. breviflora fruit and X. sagittifloium corm exhibited antihypertensive properties and ameliorate oxidative damage associated with hypertension by enhancing the antioxidant defense sysyem and inhibiting generation of free radicals.

Immunohistochemical and morphological changes associated with hepatic damage in lead acetate-induced toxicity and mitigatory properties of naringin in cockerel chicks.

Lead (Pb) toxicity constitutes a major health hazard to both humans and animals especially in the developing countries. It is a ubiquitous environmental contaminant found in the air essentially because of unregulated mining and other industrial activities. Lead can be found naturally in the soil thus, contaminating crops for human and animal food, as well as run-off water and air pollution. Intensively and extensively reared domestic chickens are exposed to contamination via inhalation and ingestion of contaminated food materials. Naringin, a product from citrus plant has been described to possess excellent metal chelating ability. Naringin is rich in flavonoid with attendant antioxidant, anti-autophagy, anti-inflammatory, hepatoprotective and cardio-nephroprotective properties. This study was conducted to investigate the hepatoprotective and modulation of oxidative stress in commercial cockerel chickens by Naringin. Thirty-six commercial cockerel chickens were randomly assigned into six groups A-F of six birds each viz: Group A served as control group while groups B, C, and D received Lead acetate at 300 ppm via drinking water continuously till the end of the experiment. In addition, groups C and D were treated with Naringin at 80 mg/kg and 160mg/kg, respectively, via oral gavage for 8 weeks. Groups E and F were administered naringin only at 80mg/kg and 160mg/kg respectively for eight weeks. Pb toxicity induced degenerative changes in the histological sections as well as, higher expression of hepatic caspase 3 as shown by immunohistochemistry. There was increased oxidative stress markers (H2O2, MDA) and depletion of the antioxidant defense system markers SOD, GPx, GSH, and GST. It concluded that Co- treatment with Naringin ameliorated oxidative stress, enhanced antioxidant defense system, reduced the expression of hepatic caspase 3 thus, offering protection against lead acetate-induced derangements in the liver of commercial cockerel chickens.

Infused aqueous curry tea extracts ameliorate Nω -Nitro-L-Arginine Methyl Ester-induced liver dysfunction in male albino Wistar rats.

BACKGROUND: Murraya koenigii (L.) Spreng. (Rutaceae) has been reported to positively affect liver function. However, the effect of M. koenigii leaves on Nω -Nitro-L-Arginine Methyl Ester (L-NAME) induced liver dysfunction is unknown. The aim of the present study was therefore to investigate the effect of M.koenigii leaves as tea on L-NAME induced liver dysfunction. METHODS: Two variants of curry tea were formulated; one was formulated entirely from leaves of M. koenigii, the other was formulated with thaumatin-rich aril obtained from seeds of Thaumatococcus danielii (Benn.) Benth. (Marantaceae). Group I animals served as control and were untreated. Groups II and V animals were administered curry tea (CT). Group III and VI animals received curry-thaumatin tea (CTT). Concurrently, L-NAME (40 mg/kg) was administered to groups IV-VI respectively for 21 days. Blood and liver samples were collected at the end of the study for biochemical, histological, and immunohistochemical analysis. RESULTS: L-NAME induced liver dysfunction evidenced by liver histology, increased activities of ALT, AST, hyperlipidemia, hepatic oxidative stress and increased hepatic NF-kB expression. Administration of CT and CTT ameliorated the L-NAME induced liver dysfunction evidenced by liver histology, increased NO hepatic bioavailability, reduced activity of ALT and AST, increased hepatic antioxidant system and decreased hepatic NF-kB expression. Thaumatin taste/flavor enhancer did not significantly reduce or potentiate the hepatoprotective, antioxidant and anti-lipidemic property of aqueous curry tea extracts in rats. CONCLUSION: L-NAME impaired liver function in rats. CT and CTT interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction. PRACTICAL APPLICATIONS: The study reports that non-selective inhibition of nitric oxide by L-NAME in rats impairs liver function and formulated curry tea types interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction in rats.

Compensatory depression of arterial pressure and reversal of ECG abnormalities by Annona muricata and Curcuma longa in hypertensive Wistar rats.

OBJECTIVES: Increasing hypertension incidence in Sub-Sahara Africa and the current cost of management of the metabolic disorder has necessitated research on medicinal plants employed in African Traditional Medicine for hypertension. Thus, this study evaluated antihypertensive effect of Annona muricata leaves or Curcuma longa rhizomes in experimentally-induced hypertensive male Wistar rats (n=70) which were unilaterally nephrectomized and daily loaded with 1% salt. Cardiovascular and haematological changes, as well as urinalysis were determined. METHODS: Rats were uninephrectomized and NaCl (1%) included in drinking water for 42 days. Extract-treated hypertensive rats were compared to normotensive, untreated hypertensive and hypertensive rats treated with lisinopril (5 mg/70 kg) or hydrochlorothiazide (12.5 mg/70 kg). A. muricata extract or C. longa extract were administered at 100, 200 or 400 mg/kg. Blood pressure (systolic, diastolic and mean arterial) and electrocardiogram was measured on day 41. Twenty-four-hour urine samples were collected from day 42. Blood samples were collected on day 43 for haematology (PCV, red cell indices, WBC and its differentials, and platelets). RESULTS: A. muricata or C. longa extracts caused a decline in elevated blood pressure of hypertensive rats. Heart rate and QT segment reduction coupled with prolonged QRS duration were reversed in extract-treated rats, with significant increases in hemogram parameters indicating increased blood viscosity. Also, leukocyturia, proteinuria and ketonuria with increased urine alkalinity, urobilinogen and specific gravity which are classical indicators of poor prognostic outcomes in hypertension were reversed in extract-treated rats. CONCLUSIONS: In conclusion, A. muricata and C. longa have cardioprotective effect with reversal of derangements in haemogram and urinalysis associated with hypertension.

Clofibrate, a Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride-Induced Toxicity.

Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride.

Antihypertensive action of Launaea taraxacifolia and its molecular mechanism of action.

Launaea taraxacifolia has been traditionally used for the management of conditions such as cardiovascular, respiratory, and metabolic diseases. High blood pressure was established by oral administration of L-Nitro Arginine Methyl Ester (L-NAME) a non-selective inhibitor of endothelial nitric oxide synthase (eNOS). The antihypertensive action of the methanol leaf extract of L. taraxacifolia was examined. Fifty male Wistar rats were divided into 5 groups of 10 animals per group: Group A (Distilled water), Group B (Hypertensive rats; 40mg/kg L-NAME), Group C (Hypertensive rats plus 100mg/kg extract), Group D (Hypertensive rats plus 200 mg/kg extract) and Group E (Hypertensive rats plus 10mg/kg of Lisinopril). The treatments were orally administered for five weeks. Haemodynamic parameters, urinalysis, indices of oxidative stress and immunohistochemistry were determined. Findings from this study showed that blood pressure parameters, urinary sodium and indices of oxidative stress increased significantly while In-vivo antioxidant defence systems decreased significantly in hypertensive rats. Immunohistochemistry revealed significant increases in expressions of mineralocorticoid receptor, angiotensin converting enzyme activity and kidney injury molecule-1 in kidney of hypertensive rats. Treatment with Launeae taraxacifolia normalized blood pressure parameters, urinary sodium, oxidative stress indices, antioxidant defence system, and serum nitric oxide bioavailability.

The therapeutic potential of the novel angiotensin-converting enzyme 2 in the treatment of coronavirus disease-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central.

Neurocognitive domains and neuropathological changes in experimental infection with Trypanosoma brucei brucei in Wistar rats.

Trypanosoma brucei brucei causes animal trypanosomiasis in several vertebrates and human African trypanosomiasis. Previous studies have only explored the incidence, clinical symptoms, haematology and biochemical changes associated with the disease. The behavioral manipulation hypothesis posits that parasites alter the behavior of host to increase the reproductive abilities of such parasites. Hence, the present study was carried out to investigate changes in behavior and cognition following experimental infection of T. brucei brucei in rat model. This study involved two groups of animals (uninfected control and T. brucei infected) with 8 rats per group. After confirmation of parasitaemia in the infected rats both groups were assessed to investigate if infection led to behavioral alterations and neuropathological changes using the open field, social interaction and forelimb suspension tests. Immunohistochemistry was performed on brain tissues using glial fibrillary acidic protein and anticalbindin-D28k, antibodies. We demonstrated that T. brucei infection triggered a significant decrease in exploratory activity, anxiety-like behavior, altered recognition of social novelty and reduced hanging latency in the hanging wire test. Immunohistochemistry revealed significant astrocytosis, loss of dendritic spines and reduction of Purkinje cell layer of the cerebellum. These results demonstrate that T. brucei infection induce signs of anxiety, impaired motor co-ordination with degeneration and loss of Purkinje cells.

D-ribose-L-cysteine prevents oxidative stress and cardiometabolic syndrome in high fructose high fat diet fed rats.

Cardiometabolic syndrome has been linked with dietary modification. Therefore, we investigated the effects of D-ribose-L-cysteine (DRLC) in rats fed with high fructose high fat (HFHF) diet. Twenty rats (n = 5), divided into 4 groups were concurrently exposed to HFHF and/or DRLC (250 mg/kg, p.o) during the 8 weeks study. The result showed that compared to control group, HFHF group had significant impairment in lipid and glucose homeostasis, increased cardiac xanthine oxidase, systolic blood pressure, heart rate, %body weight change and fluid intake. Also, there were significant reductions in HDL-C, cardiac (GPX, NO&GGT), feed intake and relative heart weight in the latter, relative to the former. However, there were no significant differences in most of the observed physical and biochemical changes in HFHF + DRLC group compared to control. DRLC alone did not disrupt the level of biomarkers. Conclusively, DRLC prevented the manifestation of oxidative stress and cardiometabolic syndrome in HFHF-diet fed rats.

Luteolin mitigates potassium dichromate-induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim-1/Nrf2 signaling pathways.

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K2 Cr2 O7 ) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K2 Cr2 O7 ), Group C (Luteolin 100 mg/kg and K2 Cr2 O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2 Cr2 O7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K2 Cr2 O7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim-1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre-treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim-1, cardiac troponin I and up-regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.

Genetic diversity of canine parvovirus variants circulating in Nigeria.

Canine parvovirus (CPV) is a fast-evolving single-stranded DNA virus that causes severe and fatal gastrointestinal disease in dogs. Lately, several mutations affecting viral protein (VP) capsid resulting in highly pathogenic variants with distinctive immunological and clinicopathological characteristics abound. This study involved screening stools of 44 randomly selected clinical cases of canine gastroenteritis from 4 cities (Ibadan, Jos, Makurdi, and Zaria) in Nigeria for CPV antigen using an on-the-spot immunoassay test kit, as well as, molecular detection of viral nucleic acid by polymerase chain reaction. Subsequently, nucleic acid sequencing of 1195-bp amplicons encompassing the VP2 encoding region was done. The resultant 40 high-quality amino acid sequences obtained were analysed for the identification and grouping of the viruses into their discrete variants - CPV-2a, CPV-2b, or CPV-2c, using key amino acids substitutions - Asn, Asp, or Glu respectively at position 426 of the VP2 gene. One-third (11/40; 27.5%) of the analysed sequences were identified as CPV-2a and two-third (29/40; 72.5%) as CPV-2c. The original CPV and CPV-2b were not detected. Also, the "new CPV-2a variant" with mutation S297A identified had two additional mutations (Y324I and T440A) associated with selective pressure and vaccination failure in their sequences. Similarly, unique CPV-2c mutants carrying genetic markers (S297A, Y324I, and Q370R) that are highly related to CPVs of Asian origin were observed. These findings revealed a high level of divergence of existing CPVs in circulation; suggesting that CPV is rapidly evolving in Nigeria lately.

Potential health benefits of zinc supplementation for the management of COVID-19 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID-19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID-19 with varying degrees of successes. Zinc possesses potential health benefits against COVID-19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID-19 pandemic. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID-19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti-inflammatory actions have become alternative to stem the tide of COVID-19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID-19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID-19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines.

Selected Antihypertensive Agents and Their Fixed-Dose Combinations Effectively Ameliorate Trastuzumab-Mediated Cardiac Dysfunction In Rats.

This study evaluates the therapeutic potentials of selected antihypertensive drugs [valsartan, amlodipine, lisinopril and their fixed-dose combinations (amlodipine + lisinopril) and (valsartan + lisinopril)] in ameliorating trastuzumab (TZM)­induced cardiac dysfunctions in experimental rats. After an ethical clearance for the study was obtained, in-bred young adult female Wistar rats were randomly allotted into 10 groups of 6 rats per group. Group I rats were treated with 10 ml/kg/day sterile water p.o. and 1 ml/kg/day sterile water i.p.; Group II, III and IV rats were orally treated with 5 mg/kg/day VAL and 1 ml/kg/day sterile water i.p., 0.25 mg/kg/day ADP and 1 ml/kg/day sterile water i.p., 0.035 mg/kg/day LSP and 1 ml/kg/day sterile water i.p., respectively. Group V rats were orally pretreated with 10 ml/kg/day of sterile water before i.p. 2.25 mg/kg/day of TZM. Groups VI-VIII rats were equally pretreated with 5 mg/kg/day VAL, 0.25 mg/kg/day ADP, and 0.035 mg/kg/day LSP before i.p. 2.25 mg/kg/day TZM treatment, respectively. Also, Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day ADP + 0.035 mg/kg/day LSP in dissolved in sterile water and 5 mg/kg/day VAL + 0.035 mg/kg/day LSP before 2.25 mg/kg/day TZM treatment for 7 days. Blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP)] and electrocardiogram (ECG) of the treated rats were measured using non-invasive procedures on days 1 and 7 of the experiment, following which the treated rats were sacrificed humanely under light inhaled diethyl ether and histopathological examination was conducted on all treated rat hearts. Results show that repeated TZM treatment significantly (p<0.05) raised SBP, DBP and MAP values from 115.0 ± 17.1 mmHg, 85.1 ± 15.1 mmHg     and      94.7 ± 15.5 mmHg, respectively on day 1      to 127.7 ± 27.8 mmHg, 87.4 ± 27.3 mmHg       and 100.5 ± 26.4 mmHg, respectively, on day 7. Oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations significantly (p<0.05) attenuated increases in the SBP, DBP and MAP values with the most significant attenuation mediated by the fixed-dose VAL + LSP combination at the SBP, DBP and MAP values of 103.8 ± 20.6        mmHg, 65.5 ± 18.8 mmHg, and 77.9 ± 18.7 mmHg, respectively. TZM treatment also profoundly (p<0.05) prolonged the QT and corrected QT intervals from 85.0 ± 11.5 ms and         161.6 ± 20.3 ms, respectively, on day 1 to 110.2 ± 21.5 ms and 226.5 ± 41.5 ms, respectively, on day 7. However, these QT and corrected QT interval prolongations were effectively and profoundly attenuated by oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, these histopathological changes were reversed with oral pretreatments with ADP, LSP, VAL and fixed-dosed [(ADP + LSP) and (VAL + LSP)] combinations although fixed-dose VAL + LSP was associated with histopathological lesions of coronary arterial wall cartilaginous metaplasia. Overall, this study revealed the promising therapeutic potentials of VAL, ADP, LSP and their fixed-dose combinations as repurposed drugs for the prevention of TZM-mediated cardiac dysfunctions.

Ramipril blunts glycerol-induced acute renal failure in rats through its antiapoptosis, anti-inflammatory, antioxidant, and renin-inhibiting properties.

OBJECTIVES: Acute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn't been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats. METHODS: Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out. RESULTS: Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group. CONCLUSIONS: The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties.

Methanol leaf extract of Momordica charantia protects alloxan-induced hepatopathy through modulation of caspase-9 and interleukin-1ß signaling pathways in rats.

BACKGROUND AND AIM: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver. MATERIALS AND METHODS: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1ß (IL-1ß) were evaluated. RESULTS: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1ß in extract-treated groups was observed. CONCLUSION: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property.