Hepatic histomorphological changes following highly active antiretroviral therapy and the intervention of hypoxis hemerocallidea in an experimental animal model.

Master of Medical Sciences in Anatomy. University of KwaZulu-Natal, Medical School 2015.Introduction Hepatotoxicity has remained a serious complication limiting the efficacy of highly active antiretroviral therapy (HAART) regimen. While this challenge continues to exist, finding possible solutions continues to attract scientific solutions. Materials and Method: Sixty- three adult male Sprague-Dawley rats were used for the study and were divided into 9 groups (A-I). Group A received HAART cocktail (Lamivudine, Stavudine & Nevirapine), Group B received HAART and H. hemerocallidea extract (100 mg/kgbw), Group C received HAART and H. hemerocallidea extract (200 mg/kgbw), 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 H. hemerocallidea extract (100 mg/kgbw), Group H received H. hemerocallidea extract (200 mg/kgbw), and Group I received water as placebo. The experiment lasted for 56 days after which, the animals were sacrificed, the liver were harvested and prepared for histological examination and blood samples were collected through cardiac puncture and centrifuged to get the serum for biochemical assessment. Results While no mortality was reported, animals treated with adjuvant HAART and AP recorded least %body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p<0.03), TG (increased p<0.03) with no change in total cholesterol levels. Adjuvant AP with HAART recorded reduced LDL (p<0.05 and 0.03), increased HDL (p<0.05) and TG (p<0.05 and 0.001). Markers of liver injury assayed showed significant increase (p<0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT were not markedly altered. Histopathological derangements ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. Conclusion The results warrant caution on the adjuvant use of H. hemerocallidea with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardio metabolic changes. More vigilant monitoring of patients at risk of antiretroviral toxicity is necessary and may prove helpful

Renal histoarchitectural changes in nevirapine therapy: possible role of kolaviron and vitamin C in an experimental animal model

Background: There is paucity of literature regarding the nephrotoxicity of antiretroviral drugs and its interaction with plantbased adjuvants. This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure of the kidneys of adult male Sprague-Dawley rats.Objective: To determine the attenuating influence of anti-oxidant status of kolaviron on the kidneys of experimental animals following nevirapine administration.Methods: Forty eight pathogen-free adult male Sprague-Dawley rats were used for this study. The animals were divided into 8 groups (A-H) with 6 animals in each group. Group A was given normal saline as the control; group B was given nevirapine; group C was given kolaviron; group D was given vitamin C; group E was given nevirapine and kolaviron; group F was given nevirapine and vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after day 28) and group H was given corn oil. The experiment lasted 56 days after which the animals were sacrificed, blood samples were collected through cardiac puncture for serum analysis and the kidneys were harvested and prepared for H&amp; E histological examination.Results: Nevirapine caused histoarchitectural damage in the glomerular apparatus with resultant increase in kidney/body weight ratio (p&lt;0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine group these parameters were significantly elevated (P&lt;0.05). However, co-administration of nevirapine and vitamin C did not improve the histoarchitecture of the kidney.Conclusion: Adjuvant treatment with kolaviron (an anti-oxidant) for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model.Keywords: Kidney, histoarchitecture, kolaviron, antiretroviral drug

Renal histoarchitectural changes in nevirapine therapy: possible role of kolaviron and vitamin C in an experimental animal model.

Background: There is paucity of literature regarding the nephrotoxicity of antiretroviral drugs and its interaction with plant-based adjuvants. This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure of the kidneys of adult male Sprague-Dawley rats. Objective: To determine the attenuating influence of anti-oxidant status of kolaviron on the kidneys of experimental animals following nevirapine administration. Methods: Forty eight pathogen-free adult male Sprague-Dawley rats were used for this study. The animals were divided into 8 groups (A-H) with 6 animals in each group. Group A was given normal saline as the control; group B was given nevirapine; group C was given kolaviron; group D was given vitamin C; group E was given nevirapine and kolaviron; group F was given nevirapine and vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after day 28) and group H was given corn oil. The experiment lasted 56 days after which the animals were sacrificed, blood samples were collected through cardiac puncture for serum analysis and the kidneys were harvested and prepared for H&amp; E histological examination. Results: Nevirapine caused histoarchitectural damage in the glomerular apparatus with resultant increase in kidney/body weight ratio (p&lt;0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine group these parameters were significantly elevated (P&lt;0.05). However, co-administration of nevirapine and vitamin C did not improve the histoarchitecture of the kidney. Conclusion: Adjuvant treatment with kolaviron (an anti-oxidant) for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model

Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners. This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols. While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes

Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners.This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols.While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes. Keywords: Liver morphology, HAART, Cytotoxicity, Stains, Biochemistry, Lipid profil