Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

Peter, Aniekan Imo,Naidu, Edwin CS,Akang, Edidiong,Ogedengbe, Oluwatosin O,Offor, Ugochukwu,Rambharose, Sanjeev,Kalhapure, Rahul,Chuturgoon, Anil,Govender, Thirumala,Azu, Onyemaechi O Korean Society of ToxicologyKorea Environmental Mu 2018 Toxicological Research Vol.34 No.3

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney

Aniekan Imo Peter,Edwin CS Naidu,Edidiong Akang,Oluwatosin O Ogedengbe,Ugochukwu Offor,Sanjeev Rambharose,Rahul Kalhapure,Anil Chuturgoon,Thirumala Govender,Onyemaechi O Azu 한국독성학회 2018 Toxicological Research Vol.34 No.3

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman’s space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Scapular length estimation from anatomical landmarks: an osteometry and radiographic evaluation using regression equations

Sunday Okon Elijah,Aniekan Imo Peter,Akpan Udo Ekanem,Innocent Asuquo Edagha 대한해부학회 2021 Anatomy & Cell Biology Vol.54 No.1

Estimation of body length has been achieved from the measurements of the scapular with relative accuracy by researches in recent times. This research hypothesized that the landmarks on the scapular and on the x-ray radiographs could be used to predict scapular length and elucidated the landmarks that best estimate the scapular length. A total of 600 scapulae and 600 anterior-posterior x-ray radiographs were used for the study. Positive correlation was observed between the measured variables and the scapular length with the males showing significantly higher mean length compared to females. The length of axillary boarder of the scapula was the best predictor of the scapular length. No significant difference (P>0.05) existed in the mean length derived from the scapular and the x-ray radiographs of scapular. We therefore conclude that measurements from the radiographs of scapular were as reliable in estimating scapular length as those from the scapular bones.

Carica papaya attenuates testicular histomorphological and hormonal alterations following alcohol‑induced gonado toxicity in male rats

Innocent A. Edagha,Ikanna E. Asuquo,Gabriel J. Ekandem,Aniekan I. Peter 한국독성학회 2020 Toxicological Research Vol.36 No.2

Chronic alcohol consumption has been implicated in male infertility, whereas Carica papaya (CP) ripe fruit possesses antioxidant activity. This study investigated histomorphological and hormonal effects of ripened CP in alcohol experimental model. Thirty Wistar rats were divided into six groups of five animals each as follows; groups 1, 2 and 3 received distilled water 2 ml, 40% ethanol 5 ml, and 40% ethanol 5 ml + 50 mg Clomiphene citrate/kg body weight, respectively, while groups 4, 5 and 6 received 40% ethanol 5 ml + CP 500, 1000 and 1500 mg/kg body weight, respectively. Sperm counts and motility were significantly decreased (p < 0.05) in group 2 compared to group 1. Testosterone significantly increased (p < 0.05) in CP-treated groups, and luteinizing hormone was significantly reduced (p < 0.05) compared to the control. Group 2 showed spermatogenic cell distortions which were ameliorated in the CP-treated groups. CP exerted testicular protective potential against ethanol-induced testicular toxicity plausibly via its antioxidant mechanism.

Ectopic Pregnancy; A Nigerian Urban Experience

( Etuknwa Bassey Tom,Frcs ),( Frcs Azu Onyemaechi Okpara ),( Peter Aniekan Imo ),( Ekandem Gabriel John ),( Bsc Olaifa Kayode ),( Aquaisua Aquaisua Nyong ),( Ikpeme Enobong ) 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.5

Objective To assess the incidence of ectopic pregnancy (EP) in St. Luke`s Hospital, Anua in Uyo metropolis, Nigeria. Data on EP incidence in developing countries are rare and often out of date, particularly in Nigeria. Methods A fi ve-year retrospective study (2000-2004) was carried out, examining all cases of EP registered in the medical fi les of records in the casualty, maternity and surgical departments of St. Luke`s Hospital, Anua in Uyo metropolis, which before the advent of the University of Uyo Teaching Hospital, in 2002, was the hub of medical activities in Akwa Ibom State. Results Within the period under study, 2,3951 pregnancies was registered in that hospital out of which 72 cases of ectopic pregnancies was reported (3/1,000 pregnancies). Most of the affected females were young single women and students with 81.9% of them between 21 and 30 years of age. Mortality was 1.4% in the study. Related risk factors included pelvic inflammatory disease, previous history of abortions, infertility and a previous history of EP. These problems are compounded by social issues leading to multiple sexual partners and fi nancial stress resulting from the palpable poverty in Nigeria today. Conclusion Reports of hospital-based incidence of EP in various centers across Nigeria varies but has increased over the last decade. Health professionals and public health offi cials in developing countries, especially those in Africa, should consider EP as a major obstetric problem for maternal morbidity. Early detection and more public education as well as advocacy programs targeted at women are needed to solve the problem of EP in Uyo, Akwa Ibom state, Nigeria.

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

Ugochukwu Offor,Edwin C. S. Naidu,Oluwatosin O. Ogedengbe,Peter I. Aniekan,Onyemaechi O. Azu 한국독성학회 2020 Toxicological Research Vol.36 No.1

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.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Oluwatosin O Ogedengbe,Ayoola I Jegede,Ismail O Onanuga,Ugochukwu Offor,Edwin CS Naidu,Aniekan I Peter,Onyemaechi O Azu 한국독성학회 2016 Toxicological Research Vol.32 No.4

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histo-morphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Ogedengbe, Oluwatosin O,Jegede, Ayoola I,Onanuga, Ismail O,Offor, Ugochukwu,Naidu, Edwin CS,Peter, Aniekan I,Azu, Onyemaechi O Korean Society of ToxicologyKorea Environmental Mu 2016 Toxicological Research Vol.32 No.4

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague-Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail-Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histo-morphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.