Vitamin E ameliorates alterations to the articular cartilage of knee joints induced by monoiodoacetate and diabetes mellitus in rats., Hassan, Waleed N., Bin-Jaliah Ismaeel, Haidara Mohamed A., Eid Refaat A., Heidar El Hassan A., Dallak Mohammad, and Al-Ani Bahjat , Ultrastructural pathology, Volume 43, Issue 2-3, p.126-134, (2019) Abstract

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 μL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA+STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly ( < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Insulin protects against hepatocyte ultrastructural damage induced by type 1 diabetes mellitus in rats, Haidara, Mohamed A., Dallak Mohammad, Heidar El Hassan A., and Al-Ani Bahjat , Ultrastructural Pathology, Volume 42, Issue 6, p. 508–515, (2018) el_hassan_a._heidar_-_ultrastructural__pathology.pdf
THE IMPACT OF ANTIOXIDANTS ON INFLAMMATION AND OXIDATIVE STRESS MARKERS IN OSTEOARTHRITIS RAT MODEL: SCANNING ELECTRON MICROSCOPE INSIGHTS, Heidar, El Hassan, Faya FareedF Al, Hassan Waleed N., Eid Refaat A., and Haidara Mohamed A. , American Journal of Pharmacology and Toxicology, Volume 9, Issue 2, p.157-167, (2014) AbstractWebsite

Osteoarthritis (OA) is characterized by degradation of matrix and destruction of articular cartilage. Articular chondrocytes are solely responsible for the production and maintenance of the extracellular matrix. Therefore, chondrocyte disruption is implicated in cartilage degeneration. Numerous studies have shown that antioxidant treatments are promising therapeutics in cases of OA. This study was designedto examine whether vitamin E protects rat articular chondrocytes against increased inflammatory markers and oxidative stress and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis rat model. Data showed that osteoarthritis group showed a significant increase in inflammatory markers, Tumor Necrosis Factor-α (TNF-α) (38±1 ng/mL), Interlukin-6 (IL-6) (253±15 ng/mL) and oxidative stress marker, Super Oxide Dismutase (SOD) (14±1 ng/mL) compared to control (18±1 ng/mL), (121+/-23 ng/mL) and (8±1 ng/mL) respectively. Opposite trend was found when animals were treated with vitamin E where TNF-α (27±2 ng/mL) and SOD (10±1 ng/mL) declined significantly. Electro-microscopic examination documented the above results and showed improvement of knee joint after administration of vitamin E. This study supported the notion that OA is a multi factorial complication, caused by inflammation and increased oxidative stress. Administration of vitamin E decreased the markers of inflammation and oxidative stress as well asimproved ultra-structure of the knee jointin acute OA animal model. However, further work id needed to validate reliability in human patients suffering from osteoarthritis.

THE IMPACT OF ANTIOXIDANTS ON INFLAMMATION AND OXIDATIVE STRESS MARKERS IN OSTEOARTHRITIS RAT MODEL: SCANNING ELECTRON MICROSCOPE INSIGHTS, Heidar, El Hassan, Faya FareedF Al, Hassan Waleed N., Eid Refaat A., and Haidara Mohamed A. , American Journal of Pharmacology and Toxicology, Volume 9, Issue 2, p.157-167, (2014) AbstractWebsite

Osteoarthritis (OA) is characterized by degradation of matrix and destruction of articular cartilage. Articular chondrocytes are solely responsible for the production and maintenance of the extracellular matrix. Therefore, chondrocyte disruption is implicated in cartilage degeneration. Numerous studies have shown that antioxidant treatments are promising therapeutics in cases of OA. This study was designedto examine whether vitamin E protects rat articular chondrocytes against increased inflammatory markers and oxidative stress and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis rat model. Data showed that osteoarthritis group showed a significant increase in inflammatory markers, Tumor Necrosis Factor-α (TNF-α) (38±1 ng/mL), Interlukin-6 (IL-6) (253±15 ng/mL) and oxidative stress marker, Super Oxide Dismutase (SOD) (14±1 ng/mL) compared to control (18±1 ng/mL), (121+/-23 ng/mL) and (8±1 ng/mL) respectively. Opposite trend was found when animals were treated with vitamin E where TNF-α (27±2 ng/mL) and SOD (10±1 ng/mL) declined significantly. Electro-microscopic examination documented the above results and showed improvement of knee joint after administration of vitamin E. This study supported the notion that OA is a multi factorial complication, caused by inflammation and increased oxidative stress. Administration of vitamin E decreased the markers of inflammation and oxidative stress as well asimproved ultra-structure of the knee jointin acute OA animal model. However, further work id needed to validate reliability in human patients suffering from osteoarthritis.

Development of a Rat Model of Knee Osteoarthritis by a Combination of Monoiodoacetate and Streptozotocin, Heidar, El Hassan A., Al-Ani Bahjat, Haidara Mohamed A., Faya Fareed Al F., Humayed Suliman Al, and Eid Refaat A. , Int. J. Morphol., Volume 35, Issue 3, p.928-935, (2017) Abstract

Osteoarthritis (OA) caused by ageing joints or as a secondary complication of diabetes is a common health problem. We sought to develop an animal model of OA induced by a combination of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA) and streptozotocin (STZ), the agent that induces diabetes mellitus. We then hypothesized that the extent of damages to the knee joint induced by this model can be greater than OA induced by either MIA or STZ. Rats were either injected with MIA (model 1) or STZ (model 2) or both agents (model 3). After 8 weeks, harvested tissues from the knee joint of these groups were examined using scanning and transmission electron microscopy. In addition, blood samples were assayed for tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) that are known to be modulated in OA and diabetes. Compared to control group, substantial damages to the articular cartilage of the knee joint were observed in the three models with the severest in model 3. In addition, rats in model 3 showed significant (P<0.0001) increase in TNF-α and IL-6 compared to model 1 and 2. Thus, we have developed a new model of knee OA in rats that mimics a type of OA that is common among elderly people who have both, “ageing” joints and diabetes.

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