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.

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.

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.

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.

Novel antihypertensive action of rutin is mediated via inhibition of angiotensin converting enzyme/mineralocorticoid receptor/angiotensin 2 type 1 receptor (ATR1) signaling pathways in uninephrectomized hypertensive rats.

Hypertension is the most common cardiovascular disease that affects approximately 26% of adult population, worldwide. Rutin is one of the important flavonoids that is consumed in the daily diet, and found in many food items, vegetables, and beverages. Uninephrectomy (UNX) of the left kidney was performed, followed by induction of hypertension. The rats were randomly divided into four groups of 10 rats: group 1-Sham-operated rats; group 2-UNX rats, group 3-UNX-L-NAME (40 mg/kg) plus rutin (100 mg/kg bwt), and groups 4-UNX-L-NAME plus lisinopril (10 mg/kg bwt), orally for 3 weeks. Results revealed significant heightening of arterial pressure and oxidative stress indices, while hypertensive rats treated with rutin had lower expressions of angiotensin converting enzyme (ACE) and mineralocorticoid receptor in uninephrectomized rats. Together, rutin as a novel antihypertensive flavonoid could provide an unimaginable benefits for the management of hypertension through inhibition of angiotensin converting enzyme and mineralocorticoid receptor. PRACTICAL APPLICATIONS: Hypertension has been reported to be the most common cardiovascular disease, affecting approximately 26% of the adult population worldwide with predicted prevalence to increase by 60% by 2025. Recent advances in phytomedicine have shown flavonoids to be very helpful in the treatment of many diseases. Flavonoids have been used in the treatment and management of cardiovascular diseases, obesity and hypertension. The study revealed that rutin, a known flavonoid inhibited angiotensin converting enzyme (ACE), angiotensin 2 type 1 receptor (ATR1), and mineralocorticoid receptor (MCR), comparable to the classic ACE inhibitor, Lisinopril, indicating the novel antihypertensive property of rutin. Therefore, flavonoids such as rutin found in fruits and vegetables could, therefore, serve as an antihypertensive drug regimen. Combining all, functional foods rich in flavonoids could be used as potential therapeutic candidates for managing uninephrectomized hypertensive patients.