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.

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.

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.

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.

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.

Effectiveness of Mavrilimumab in Viral Infections Including SARS-CoV-2 Infection - A Brief Review

Bhatt Kinal,Garimella Radhika,Taugir Rahima,Mehta Isha,Jamal Muhammad,Vijayan Rupalakshmi,Offor Rita,Nwankwo Kanayo,Arif Uroosa,Waheed Khurram,Kumari Priyanka,Lathiya Maulik,Michel George,Pandya Naush 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.1

Hyperinflammation and cytokine storm has been noted as a poor prognostic factor in patients with severe pneumonia related to coronavirus disease 2019 (COVID-19). In COVID-19, pathogenic myeloid cell overactivation is found to be a vital mediator of damage to tissues, hypercoagulability, and the cytokine storm. These cytokines unselectively infiltrate various tissues, such as the lungs and heart, and nervous system. This cytokine storm can hence cause multi-organ dysfunction and life-threatening complications. Mavrilimumab is a monoclonal antibody (mAb) that may be helpful in some cases with COVID-19. During an inflammation, Granulocyte-macrophage colony-stimulating factor (GM-CSF) release is crucial to driving both innate and adaptive immune responses. The GM-CSF immune response is triggered when an antigen attaches to the host cell and induces the signaling pathway. Mavrilimumab antagonizes the action of GM-CSF and decreases the hyperinflammation associated with pneumonia in COVID-19, therefore strengthening the rationale that mavrilimumab when added to the standard protocol of treatment could improve the clinical outcomes in COVID-19 patients, specifically those patients with pneumonia. With this review paper, we aim to demonstrate the inhibitory effect of mavrilimumab on cytokine storms in patients with COVID-19 by reviewing published clinical trials and emphasize the importance of extensive future trials.

Sepsis-induced cardiomyopathy is associated with higher mortality rates in patients with sepsis

Balaram Krishna J Hanumanthu,Anika Sasidharan Nair,Adarsh Katamreddy,Jason S Gilbert,Jee Young You,Obiageli Lynda Offor,Ankit Kushwaha,Ankita Krishnan,Marzio Napolitano,Leonidas Palaidimos,Joaquin Mor 대한중환자의학회 2021 Acute and Critical Care Vol.36 No.3

Background Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC. Methods In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echo and was defined by a new onset decline in left ventricular ejection fraction (LVEF) ≤50%, or ≥10% decline in LVEF compared to baseline in patients with a history of heart failure with reduced ejection fraction. Multivariable logistic regression analysis was performed using the R software program. Results Of the 359 patients in the final analysis, 19 (5.3%) had SIC. Eight (42.1%) of the 19 patients in the SIC group and 60 (17.6%) of the 340 patients in the non-SIC group died during hospitalization. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15–18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23–0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24–55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients. Conclusions SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.