Evaluation of tenofovir disoproxil fumarate loaded silver nanoparticle on testicular morphology in experimental type-2 diabetic rats.

Reproductive derangement and metabolic disorders in human immunodeficiency virus (HIV) infected persons require a nanoparticle delivery system to convey antiretroviral drugs to the anatomical sanctuary such as testis. This study investigated the effects of tenofovir disoproxil fumarate (TDF) loaded silver nanoparticles (AgNPs) on the testicular oxidative stress, inflammatory cytokines and histology in male diabetic rats. Thirty-six Sprague-Dawley rats weighing 230 ± 20 g were randomly divided into diabetic and non-diabetic groups (n = 18). Diabetes was induced using the fructose-streptozotocin (Frt-STZ) rat model. Both groups were further divided into three (n = 6) and administered distilled water, TDF, or TDF-AgNP. Results obtained with the TDF-AgNP administration showed a significant increase (p < .05) in the reduced glutathione and catalase levels. Tumour necrosis factor-alpha and interleukin 6 were reduced in diabetic rats administered TDF-AgNP. More so, administration of TDF-AgNP to diabetic rats improved testicular histoarchitecture in diabetic rats. In addition, diabetic rats administered TDF-AgNP showed a significant reduction (p < .05) in blood glucose levels. TDF-AgNP to diabetic rats enhanced testicular antioxidant enzyme, reduced testicular inflammation, and alleviated structural derangements in the testis. Thus, the application of AgNP to deliver TDF may alleviate testicular toxicity and subsequently cater for neglected reproductive dysfunction during the management of HIV infection.

Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex in diabetic rats.

Tenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1ß) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1ß concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles' antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration.

Highly active antiretroviral therapy conjugated silver nanoparticle ameliorates testicular injury in type-2 diabetic rats.

Despite advances in managing human immunodeficiency virus (HIV) infection and success in the treatment prognosis using highly active antiretroviral therapy (HAART). The clinical efficacy of this regimen has been associated with increased adverse effects such as metabolic derangements and reproductive dysfunctions. These adverse effects necessitate a nanoparticle delivery vehicle like silver nanoparticles (AgNPs), a multi-functional drug delivery system, to transport the HAART to the viral reservoir site like testis. This study was therefore designed to evaluate the effects of HAART loaded AgNPs (HAART-AgNPs) on testicular oxidative stress markers, an inflammatory biomarker, and histomorphology in a rat model of diabetes. Thirty-six adult male Sprague-Dawley rats were randomly divided into two groups (n = 18) non-diabetic and fructose-streptozotocin (Frt-STZ) induced type 2 diabetes (T2DM). Thereafter, both groups were subdivided into three (n = 6) and treated with distilled water, HAART and HAART-AgNPs. HAART-AgNPs caused a significant increase (p < 0.05) in catalase (23.43 ± 0.92) level vs diabetic control (16.95 ± 1.04). Also, HAART-AgNP caused a significant reduction (p < 0.05) in malondialdehyde, interleukin-6 and blood glucose levels (1.94 ± 0.06, 93.65 ± 3.6, 287.33 ± 22.85 respectively), compared to their respective diabetic control values (2.18 ± 0.12, 143.4 ± 9.2, 372.16 ± 23.16). Furthermore, HAART-AgNPs mitigated tubular atrophy, basement membrane thickening, interstitial distension, fibrous elemental distortion and peri-interstitial tissue alterations in the testis of diabetic rats. The results from this study showed that administration of HAART-AgNPs to diabetic rats reduced testicular inflammation, improved glycaemic control, antioxidant status, and testicular histology. Therefore, conjugation of AgNP with HAART may cater for the reproductive dysfunction during the management of HIV infection.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection: Microbiologic perspectives and anatomic considerations for sanctuary sites.

INTRODUCTION: A significant chunk of global life - the economy, sports, aviation, academic, and entertainment activities - has significantly been affected by the ravaging outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) with devastating consequences on morbidity and mortality in many countries of the world. METHODS: This review utilized search engines such as google scholar, PubMed, ResearchGate, and web of science to retrieve articles and information using keywords like "Coronavirus", "SARS-CoV-2", "COVID-19", "Origin of coronavirus and SARS-CoV-2", "microbiology of coronavirus", "microbiology of SARS-CoV-2", COVID-19", "Coronavirus reservoir sites", "Anatomic sanctuary sites and SARS-CoV-2", biological barriers and coronavirus", biological barrier and SARS-CoV-2". RESULTS: While this pandemic has caught the global scientific community at its lowest level of preparedness, it has inadvertently created a unified and wholesome approach towards developing potential vaccine (s) candidates by escalating clinical trial protocols in many countries of Europe, China and the United States. Interestingly, viral pathobiology continues to be an evolving aspect that potentially shows that the management of the current outbreak may largely depend on the discovery of a vaccine as the administration of known antiviral drugs are proving to offer some respite. Unfortunately, discontinuation and longtime administration of these drugs have been implicated in endocrine, reproductive and neurological disorders owing to the development of pathological lesions at anatomical sanctuary sites such as the brain and testis, as well as the presence of complex biological barriers that permit the entry of viruses but selective to the entrance of chemical substances and drugs. CONCLUSION: This review focuses on the microbiologic perspectives and importance of anatomical sanctuary sites in the possible viral rebound or reinfection into the system and their implications in viral re-entry and development of reproductive and neurological disorders in COVID-19 patients.

Hypoxis hemerocallidea alters metabolic parameters and hepatic histomorphology in streptozotocin-nicotinamide-induced diabetic male rats under antiretroviral therapy.

INTRODUCTION: Highly active antiretroviral therapy (HAART) and HIV/AIDS have been demonstrated to induce endocrine/metabolic dysfunction with a consequential increase in morbidity/mortality due to organ toxicities. This study aimed at investigating the possible protective effect of Hypoxis hemerocallidea (HH) against metabolic and hepatic histomorphology of diabetic rats under HAART. MATERIAL AND METHODS: Sixty-two adult male Sprague-Dawley rats were divided into a normoglycemic group A (n = 6) and 7 diabetic (110 mg/kg nicotinamide + 45 mg/kg streptozotocin) groups (B-H) (n = 8) and treated according to protocols. Concomitant treatment with adjuvant HH and HAART resulted in the least %body weight gain as the liver weight decreased in all treated animals. RESULTS: Significant changes in serum lipids were aggravated by treatment with HH and HAART, triglycerides and total cholesterol levels were elevated (p < 0.001/0.05), but changes in high-density lipoprotein (HDL) and total protein levels were insignificant. While artherosclerotic and cardiopulmonary indexes remained insignificant, concomitant use of HH with HAART in diabetes resulted in reduction of low-density lipoprotein (LDL) (p < 0.001), and increased triglyceride (p < 0.05) and total cholesterol (p < 0.001). The parameters of liver injury showed a significant (p < 0.05) increase in ALT of animals treated with HH alone, HAART + HH and melatonin; however, an insignificant decline in AST level was recorded. Treatment with adjuvant HAART, HH and melatonin resulted in significant (p < 0.005/0.0001) up-regulation of ALP and total bilirubin levels. Histopathology derangement ranged from severe hepatocellular distortions, necrosis with reduced glycogen expression following co-treatment of HAART+melatonin, HH and HAART alone in diabetes. CONCLUSIONS: Presumptive hypoglycemic use of HH with HAART by people living with HIV/AIDS requires caution as implications for hepatocellular injuries are suspected with further uncontrolled metabolic disorder.

Momordica charantia mitigates hepatic injury following adjuvant treatment with antiretroviral drugs in diabetic animal models.

Momordica charantia (M. charantia) is a medicinal plant, used in traditional practice for treating diseases like hypertension and diabetes mellitus. This study investigated the possible hepato-protective effect of M. charantia following treatment with highly active antiretroviral therapy (HAART) in diabetic rats. 48 adult male Sprague Dawley rats were divided into seven groups (A-G) of 7 animals per group and treated according to protocols. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection (45 mg/kg body weight). The animals were euthanized on the 10th week with liver removed for examination and blood obtained via cardiac puncture and centrifuged to collect the sera. Blood glucose levels (BGL) were consistently and significantly raised (p < 0.05) in all groups not receiving the adjuvant M. charantia. Treatment with M. charantia reverses the increase in BGL to near normal. Markers of liver injury assayed showed significant increase (p < 0.05) in AST, ALP and ALT levels in groups not receiving M. charantia. Adjuvant HAART and M. charantia caused significant declines in the liver enzymes (p < 0.05). Serum GGT was not markedly altered. Treatment with M. charantia significantly restored liver enzymes elevations to near normal comparable to control. Histopathological observations ranged from severe hepatocellular distortions, necrosis and massive fibrosis following treatment of HAART in diabetic groups not receiving M. charantia. Treatment with M. charantia did not show any sign of hepatotoxicity as judged from the histological and biochemical observations.

Antiretroviral Therapy and Alcohol Interactions: X-raying Testicular and Seminal Parameters Under the HAART Era.

The prevalence of alcohol use among HIV-infected patients undergoing antiretroviral (ARV) treatments has raised several concerns related to key therapeutic indices. These include drug interactions, compliance, efficacy and toxicity with the possibility of accelerated disease progression. Interaction of ARVs with alcohol can result in therapeutic failures or place patients at significant risk for toxicities. Research findings in this particular area are, however, limited and sometimes conflicting. This review focuses on alcohol and ARV interactions affecting testicular and spermatogenic indices. Antiretroviral drugs are known to negatively impact testicular functions via altered mitochondrial DNA and oxidative stress mechanisms. Interaction with alcohol can significantly affect seminal fluid concentration of ARVs. Habitual consumption of alcohol causes testicular hypofunction with potential for lowered fertility. Concomitant use of ARVs appears to act synergistically to exacerbate this toxicity. Alcohol also induces cytochrome P450 (CYPs) microsomal enzymes, which in turn affect ARVs metabolized by these enzymes. In the presence of ARVs with strong inhibitory activity, increased bioavailability with toxicities predominates. In addition, alcohol and ARVs have pronounced effects on membrane-associated drug transporters. Alcohol alters the properties of the lipid bilayer by changing membrane permeability and protein distribution. Since drug transporters critical to pharmacokinetics are integral membrane proteins, alcohol tends to diminish the activity of both the efflux and influx transporters. While excessive alcohol precipitates accelerated hypogonadism, future research needs to be directed to quantifying these effects of alcohol and ARVs in human testicular tissue.

Does Hypoxis hemerocallidea mitigate renal histopathological injuries following highly active antiretroviral therapy? An experimental animal study.

BACKGROUND: Nephrotoxicity has become an important public health problem following the success recorded with highly active antiretroviral therapy, and there is paucity of literature reporting the attenuating influence of plant-based adjuvants that can mitigate the effects. METHODS: Sixty three adult male Sprague-Dawley rats were divided into 9 groups (A-I) and treated as follows: group A received HAART cocktail (lamivudine, stavudine and nevirapine), group B received HAART and Hypoxis hemerocallidea (HH) extract (200 mg/kg), group C received HAART and HH (100 mg/kg), group D received HAART and vitamin C, group E received HAART and vitamin E, group F received HAART, vitamin C and vitamin E, group G received HH extract (100 mg/kg), group H received HH extract (200 mg/kg), and group I received saline as placebo. After 56 days, animals were euthanized, kidneys harvested and prepared for H&E staining and blood samples were collected for BUN and serum creatinine analyses. RESULTS: The results from histological slides showed distorted glomerular and epithelial components with extensive loss of Bowman's capillary integrity in HAART-treated group. Adjuvant treatment with HH both high and low doses did not show any remarkable attenuating influence. However, HH100mg/kg-alone treated group showed improved histological layout as compared to the higher dose. Co-administration of HAART and vitamins C and E did not improve the parameters examined. The serum creatinine and BUN levels were significantly increased (P<0.05) following HAART with observable increase in kidney body weight ratio. SCR levels in group D was significantly reduced (P<0.05) but elevated in groups B, C, G and H (P<0.001). Groups B and C, as well as groups F and H recorded higher BUN values (P<0.05). CONCLUSIONS: Adjuvant treatment with HH extract did not attenuate the nephrotoxicity of HAART in this model.