Molecular and Histopathological Study on the Ameliorative Impacts of Petroselinum Crispum and Apium Graveolens against Experimental Hyperuricemia.

Hyperuricemia is an abnormal metabolic condition characterized by an increase in uric acid levels in the blood. It is the cause of gout, manifested by inflammatory arthritis, pain and disability. This study examined the possible ameliorative impacts of parsley (PAR) and celery (CEL) as hypouricemic agents at biochemical, molecular and cellular levels. PAR and CEL alone or in combination were orally administered to hyperuricemic (HU) mice and control mice for 10 consecutive days. Serum levels of uric acid and blood urea nitrogen (BUN), xanthine oxidase activity, antioxidants, inflammatory (IL-1ß and TNF-α) and anti-inflammatory cytokines (IL-10) were measured. mRNA expression of urate transporters and uric acid excretion genes in renal tissues were examined using qRT-PCR (quantitative real time PCR). Normal histology and immunoreactivity of transforming growth factor-beta 1 (TGF-ß1) in kidneys was examined. Administration of PAR and CEL significantly reduced serum BUN and uric acids in HU mice, ameliorated changes in malondialdehyde, catalase, and reduced glutathione, glutathione peroxidase (GPX), IL-1ß, TNF-α and IL-10 in hyperuricemic mice. Both effectively normalized the alterations in mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expression, as well as changes in TGF-ß1 immunoreactivity. Interestingly, combined administration of PAR and CEL mitigated all examined measurements synergistically, and improved renal dysfunction in the hyperuricemic mice. The study concluded that PAR and CEL can potentially reduce damaging cellular, molecular and biochemical effects of hyperuricemia both individually and in combination.

Protective Impacts of Moringa oleifera Leaf Extract against Methotrexate-Induced Oxidative Stress and Apoptosis on Mouse Spleen.

OBJECTIVE: The current study was aimed to examine the possible ameliorative impacts of MO leaf extract (MOLE) against MTX-induced alterations on oxidative stress of mouse spleen and explore the possible molecular mechanism that controls such impacts. METHODS: Adult male mice were allocated into 4 groups: control, Moringa oleifera leaf extract (MOLE), MTX, and MOLE plus MTX. Mice received MOLE orally for a week before MTX injection and continued for 12 days. Serum and spleen were sampled for biochemical and quantitative gene expressions. RESULTS: As compared with the MTX-injected group, MOLE effectively reduced the changes in total proteins, spleen MDA, SOD and catalase activities, and changes in serum antioxidants levels. Moreover, there is downregulation of antioxidant genes (SOD and catalase) and antiapoptotic genes (XIAP and Bcl-xl) along with upregulation in Bax and caspase-3 mRNA (apoptotic genes) in the MTX-injected group. MTX induced changes in IL-1ß, IL-6, TNF-α, and IL-10 expression. MOLE restored and ameliorated the changes induced in biochemical, antioxidants, apoptosis, and apoptosis associated genes that were induced by MTX intoxication. CONCLUSION: Current findings indicated that pretreatment with MOLE to MTX-intoxicated mice showed the potential usage of MO for oxidative stress and apoptosis treatment.

The ameliorative impacts of Moringa oleifera leaf extract against oxidative stress and methotrexate-induced hepato-renal dysfunction.

Moringa Oleifera (MO) is a herbal plant native to South Asia known for its anti-oxidative and anti-inflammatory properties. This study explored the protective effects of MO leaf extract (MOLE) against oxidative stress and hepatic and renal injuries caused by methotrexate (MTX) therapy. Mice received a single intraperitoneal injection of 20 mg/kg body weight MTX to induce hepatic and kidney injuries. They then received 300 mg/kg body weight of MOLE orally for seven days, followed by MTX on day 7 then five more days of MOLE (12 days total). Blood, liver and kidney samples were collected from all groups and the following biochemical parameters were tested: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase, superoxide dismutase (SOD), malondialdehyde (MDA) and total proteins. Quantitative real time PCR (qRT-PCR) was used to examine Nrf2, HO-1, BAX, TIMP, XIAP, and NFkB, which are associated with apoptosis, anti-apoptosis and oxidative stress. Capase-9 and Bcl2 genes underwent immunohistochemical analysis. Pretreatment with MOLE reduced the effect of MTX on ALT, AST and total proteins, and reversed its effect on serum and tissue antioxidants. Nrf2/HO-1, apoptotic and anti-apoptotic gene expression was regulated, and Bax and TIMP were reduced; XIAP expression was increased in both the liver and kidney samples, and immunoreactivity of caspase-9 and Bcl2 was restored in the MOLE-administered experimental group. Overall, the study concluded that MOLE can inhibit the effects of hepato-renal injuries caused by MTX by regulating oxidative stress, apoptosis and anti-apoptotic genes at biochemical, molecular and cellular levels.