Mr. Kamal Hassan Kader Anatomy Laboratory Technician, Basic Medical Sciences Department College of Medicine, Ajman University Mr. Kamal Hassan Kader is an accomplished Anatomy Laboratory Technician in the Basic Medical Sciences Department at the College of Medicine, Ajman University. He earned his Diploma in Medical Laboratory Technology from the Rev. Borten Memorial Institute of Clinical Technology, Tamil Nadu, India. Mr. Kamal began his career as a Medical Laboratory Technician in various hospitals across India before transitioning to academia. He served as a Histology Laboratory Technician at the College of Medicine, Rajah Muthiah Medical College, Chidambaram, Tamil Nadu, India. He later joined the College of Medicine at Al Arab Medical University, Benghazi, Libya, as a Histology Technician. Mr. Kamal subsequently moved to the United Arab Emirates, where he worked as an Anatomy Laboratory Technician at the Gulf Medical University (GMU), Ajman, and later as a Research Assistant at the College of Medicine, United Arab Emirates University (UAEU), Al Ain, Abu Dhabi. During his tenure at UAEU, he contributed to several research publications and scientific posters presented in reputed journals and conferences. Before joining Ajman University, Mr. Kamal served as an Anatomy Laboratory Technician at the Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Healthcare City, Dubai, UAE. He has also gained extensive experience as a Surgical Skills Technician at the Surgical Skills Laboratories of both GMU and MBRU. His expertise includes the thawing, preservation, and preparation of imported fresh frozen human anatomical specimens for brain, neuro-spinal, cervical, and orthopedic surgical workshops and conferences, organized in collaboration with national and international medical associations.
Abstract In this study, the hepatoprotective and anti-fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl4)-induced liver fibrosis in mice. CCl4 administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl4 produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase-1 expression, antioxidant defenses, and accumulation of 4-hydroxynonenal and 3-nitrotyrosine. Furthermore, CCl4 administration evoked profound expression of pro-inflammatory cytokine expressions such as tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-1β in hepatic tissues, which corroborated with nuclear factor κB activation. Additionally, CCl4-treated animals exhibited higher apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and poly (ADP-ribose) polymerase activation. Moreover, histological and biochemical investigations revealed marked fibrosis in the livers of CCl4-administered animals. However, NTK treatment mitigated CCl4-induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti-fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.
Abstract Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1. In addition, GP attenuated the CP-induced oxidative/nitrative stress by suppressing the activation of NADPH oxidase, augmenting the endogenous antioxidant defense system, and diminishing the accumulation of 4-hydroxynonenal and 3-nitrotyrosine in renal tissues. Furthermore, reduced levels of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta indicated that CP-induced renal inflammation was mitigated upon the treatment with GP. GP also attenuated the CP-induced activation of mitogen-activated protein kinases, excessive activities of caspase-3/7 and poly (ADP-ribose) polymerase, DNA fragmentation, and apoptosis. When administered 12 h after the onset of kidney injury, GP showed a therapeutic effect by ameliorating CP-induced nephrotoxicity. Moreover, GP synergistically enhanced the CP-induced cell death of T24 human bladder cancer cells. Collectively, our data indicate that GP attenuated the CP-induced renal tissue injury by abrogating oxidative/nitrative stress and inflammation and by blocking cell death pathways, thereby improving the renal function. Thus, our results suggest that the use of GP may be a promising new protective strategy against cisplatin-induced nephrotoxicity.
DMF has been recently approved for the treatment of multiple sclerosis. DMF elicits anti-inflammatory actions via activation of Nrf-2 cascade. However, the DMF effects on mitigating the pathophysiology of diabetic retinopathy (DRP) are hitherto unknown. Hence, we have investigated the retinal cytoprotective effects of DMF, by employing a murine model of DRP. Results showed that Nrf-2 activation and its down-stream targets such as hemeoxygenase-1 (HO-1), thioredoxin reductase 1 (TXNRD1) and glutamate-cysteine ligase modifier (GCLM) expressions were diminished in the diabetic retinas (DR) as determined by western blot assay. Further increased oxidative stress (Elevated NADPH oxidase activity, diminished SOD activity, GSH levels and elevated lipid peroxides accumulation) were noted in the DR. Elevated levels of pro-inflammatory cytokines (TNF alpha, IL-1beta and MCP-1) and adhesion molecules (ICAM-1 and VCAM-1) were also observed in the DR. Next, greater degree of retinal apoptosis was seen in the DR as determined by TUNEL staining, caspase 3 and poly (ADP-ribose) polymerase [PARP] activities. Further, increased vascular permeability was observed in DR as determined by FITC-dextran perfusion studies. All the above diabetic phenotypic insults to the retina were attenuated upon treatment with DMF. In addition, high glucose [HG] induced superoxide production, NF-kB, RhoA activation, pro-inflammatory cytokines expression and adhesion of THP-1 monocytes to human retinal endothelial cells [HREC] was blunted upon treatment with DMF. Moreover, cytoprotective effects of DMF against HG induced phenotypic changes in HREC and retinal ganglion cell apoptosis were abrogated upon genetic silencing of Nrf-2. In sum, our observations unequivocally demonstrate the retinal cytoprotective effects of DMF in diabetic milieu and it could be repurposed for future clinical utility in the management of diabetic retinopathy. Supported By: American Diabetes Association (1-15-BS-018 to L.C.); United Arab Emirates University
Activation of N-SMase results in the generation of pro-apoptotic/inflammatory bioactive ceramide species via hydrolysis of sphingomyelin. However, the precise role of N-SMase in the pathogenesis of diabetic retinal tissue injury is not yet defi ned and hence this forms the premise of our study. Diabetic animals were treated with N-SMase inhibitor - GW4869 (10 mg/kg/day) for 14 weeks. Results indicated that N-SMase activity and protein levels were significantly increased in the diabetic retinal tissues, with concordant accumulation of ceramides. Increased NADPH oxidase activity, diminished SOD activity, GSH content and elevated lipid peroxide (4-Hydroxynonenal) accumulation were noted in the diabetic retinas. Similar trend was observed with the levels of pro-inflammatory cytokines (TNF-alpha, IL-1 beta and MCP1) and adhesion molecules (ICAM-1 and VCAM-1) in the diabetic retinas. Further, higher degree of apoptosis was observed in the diabetic retinal tissues as revealed by TUNEL staining, Caspase 3 and poly (ADP-ribose) polymerase [PARP] activities. Further there was also marked activation of mitogen activated protein kinases (MAPKs) in the diabetic retinas as determined by Western blot. The above phenotypic changes inflicted by diabetes to the retina were mitigated upon inhibition of N-SMase. In addition, high glucose induced NF-kB activation and pro-inflammatory cytokine expression and adhesion of THP-1 monocytes to human retinal endothelial cells was blunted upon treatment with GW4869 or silencing of N-SMase-2. Similarly high glucose induced apoptosis of rat retinal Müller cells was attenuated upon treatment with GW4869 or silencing of N-SMase-2. Collectively our findings establish the pivotal role of N SMase in the pathogenesis of diabetic retinal tissue injury. Inhibition of N-SMase could be pursued as novel cytoprotective strategy for the management of diabetic retinopathy. Supported By: United Arab Emirates University