Therapeutic Versus Preventative Use of Ginkgo biloba Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice.

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761's antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention.

Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats.

BACKGROUND: Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation. METHODS: The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME. RESULT: Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects. CONCLUSIONS: These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.

Role of cAMP/pCREB and GSK-3ß/NF-κB p65 signaling pathways in the renoprotective effect of mirabegron against renal ischemia-reperfusion injury in rats.

Acute kidney injury and other renal disorders are thought to be primarily caused by renal ischemia-reperfusion (RIR). Cyclic adenosine monophosphate (cAMP) has plenty of physiological pleiotropic effects and preserves tissue integrity and functions. This research aimed to examine the potential protective effects of the ß3-adrenergic receptors agonist mirabegron in a rat model of RIR and its underlying mechanisms. Male rats enrolled in this work were given an oral dose of 30 mg/kg mirabegron for two days before surgical induction of RIR. Renal levels of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), cAMP, cAMP-responsive element binding protein (pCREB), and glycogen synthase kinase-3 beta (GSK-3ß) were assessed along with blood urea nitrogen and serum creatinine. Additionally, caspase-3 and nuclear factor-kappa B (NF-κB) p65 were explored by immunohistochemical analysis. Renal specimens were inspected for histopathological changes. RIR led to renal tissue damage with elevated blood urea nitrogen and serum creatinine levels. The renal KIM-1, MCP-1, TNF-α, and GSK-3ß were significantly increased, while IL-10, cAMP, and pCREB levels were reduced. Moreover, upregulation of caspase-3 and NF-κB p65 protein expression was seen in RIR rats. Mirabegron significantly reduced kidney dysfunction, histological abnormalities, inflammation, and apoptosis in the rat renal tissues. Mechanistically, mirabegron mediated these effects via modulation of cAMP/pCREB and GSK-3ß/NF-κB p65 signaling pathways. Mirabegron administration could protect renal tissue and maintain renal function against RIR.

Cyclosporine-induced kidney damage was halted by sitagliptin and hesperidin via increasing Nrf2 and suppressing TNF-α, NF-κB, and Bax.

Cyclosporine A (CsA) is employed for organ transplantation and autoimmune disorders. Nephrotoxicity is a serious side effect that hampers the therapeutic use of CsA. Hesperidin and sitagliptin were investigated for their antioxidant, anti-inflammatory, and tissue-protective properties. We aimed to investigate and compare the possible nephroprotective effects of hesperidin and sitagliptin. Male Wistar rats were utilized for induction of CsA nephrotoxicity (20 mg/kg/day, intraperitoneally for 7 days). Animals were treated with sitagliptin (10 mg/kg/day, orally for 14 days) or hesperidin (200 mg/kg/day, orally for 14 days). Blood urea, serum creatinine, albumin, cystatin-C (CYS-C), myeloperoxidase (MPO), and glucose were measured. The renal malondialdehyde (MDA), glutathione (GSH), catalase, and SOD were estimated. Renal TNF-α protein expression was evaluated. Histopathological examination and immunostaining study of Bax, Nrf-2, and NF-κB were performed. Sitagliptin or hesperidin attenuated CsA-mediated elevations of blood urea, serum creatinine, CYS-C, glucose, renal MDA, and MPO, and preserved the serum albumin, renal catalase, SOD, and GSH. They reduced the expressions of TNF-α, Bax, NF-κB, and pathological kidney damage. Nrf2 expression in the kidney was raised. Hesperidin or sitagliptin could protect the kidney against CsA through the mitigation of oxidative stress, apoptosis, and inflammation. Sitagliptin proved to be more beneficial than hesperidin.

Systemic and topical Ginkgo biloba leaf extract (Egb-761) ameliorated rat paw inflammation in comparison to dexamethasone.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo Biloba leaf extract (Egb-761) is used for treating various inflammatory disease conditions therefore this study was performed. AIM OF THE STUDY: The present study aimed at comparing the ameliorative effects of both systemic and topical Egb-761 versus dexamethasone on carrageenan-induced hind paw inflammation in rats. MATERIAL AND METHODS: Wistar albino rats were injected with carrageenan solution in the sub-planter region of the right hind paw. Egb-761 and dexamethasone were administered systemically to two groups while Egb-761 ointment 2% and dexamethasone sodium phosphate ointment were applied topically for another two groups. Vernier Caliper was used to assess rat paw thickness. Tissue malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) levels have been estimated. RESULTS: Carrageenan induced a significant rat paw edema and inflammation noticed 1 h post-injection as well as an increase of MDA, NO, and TNF-α in the inflamed skin tissues compared to the control group. Systemic and topical administration of Egb-761 and dexamethasone resulted in a significant reduction in carrageenan-induced rat paw edema. They reduced the tissue levels of MDA, NO, and TNF-α. Dexamethasone showed a little bit superior anti-inflammatory and antioxidant efficacy over Egb-761. CONCLUSION: Our findings indicate the possibility of the therapeutic value of Egb-761 for alleviation of local inflammation by attenuating the increased MDA, NO and TNF-α levels.

Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice.

It's crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Therapeutic Potential of Mesenchymal Stem Cells versus Omega n - 3 Polyunsaturated Fatty Acids on Gentamicin-Induced Cardiac Degeneration.

This study compared the cardioprotective action of mesenchymal stem cells (MSCs) and PUFAs in a rat model of gentamicin (GM)-induced cardiac degeneration. Male Wistar albino rats were randomized into four groups of eight rats each: group I (control group), group II (gentamicin-treated rats receiving gentamicin intraperitoneally (IP) at dose of 100 mg/kg/day for 10 consecutive days), group III (gentamicin and PUFA group receiving gentamicin IP at dose of 100 mg/kg/day for 10 consecutive days followed by PUFAs at a dose of 100 mg/kg/day for 4 weeks), and group IV (gentamicin and MSC group receiving gentamicin IP at dose of 100 mg/kg/day followed by a single dose of MSCs (1 × 106)/rat IP). Cardiac histopathology was evaluated via light and electron microscopy. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), caspase-3 (apoptosis), Bcl2, and Bax expression was performed. Moreover, cardiac malonaldehyde (MDA) content, catalase activity, and oxidative stress parameters were biochemically evaluated. Light and electron microscopy showed that both MSCs and PUFAs had ameliorative effects. Their actions were mediated by upregulating PCNA expression, downregulating caspase-3 expression, mitigating cardiac MDA content, catalase activity, and oxidative stress parameters. MSCs and PUFAs had ameliorative effects against gentamicin-induced cardiac degeneration, with MSCs showing higher efficacy compared to PUFAs.

Anatabine attenuates ovalbumin-induced asthma via oxidative stress and inflammation mitigation and Nrf2/HO-1 signaling upregulation in rats.

AIMS: Asthma affects a large number of people worldwide and is characterized by chronic allergic airway inflammation. Anatabine is a natural alkaloid that is structurally similar to nicotine and found in the Solanaceae family of plants, with anti-inflammatory properties. Consequently, this study aimed to evaluate the potential therapeutic effect of anatabine against asthma. MAIN METHODS: Ovalbumin was used to induce asthma in rats. Two asthmatic groups were treated with low and high doses of anatabine. KEY FINDINGS: Asthmatic animals experienced increased total leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF), bronchitis, and bronchopneumonia associated with mast cell infiltration. Additionally, inducible nitric oxide synthase immunostaining was observed, with decreased pulmonary antioxidant capacity and enzymes and decreased Nrf2 and HO-1 gene expression while increased NFκB-P65 expression. Interestingly, asthmatic animals treated with anatabine at both doses showed dose-dependently decreased inflammatory cells and cytokine levels within BALF reduced inflammation in the airways through decreased mast cell infiltration within lung tissues and increased antioxidant enzymes and Nrf2 and Ho-1 expression levels. SIGNIFICANCE: Our results highlight the potential beneficial effect of anatabine against asthma through anti-inflammatory and antioxidant mechanisms. Therefore, anatabine is a promising candidate for pulmonary asthma treatment.

Valproate attenuates hypertonic glycerol-induced rhabdomyolysis and acute kidney injury.

BACKGROUND AND AIM: The current study investigated the effects of treatment with 300 mg/kg valproic acid on rhabdomyolysis and acute kidney injury induced by intramuscular injection of hypertonic glycerol in rats. METHODS: Four groups of male wistar rats: control and hypertonic glycerol, valproic acid and valproic acid + hypertonic glycerol treated groups were used. Blood urea nitrogen, serum creatinine, creatinine kinase (CK) and CK MB, myoglobin and renal reduced glutathione (GSH) levels were measured. Histopathological examination of the kidneys was carried out to evaluate the degree of renal injury in each group. The expression of interleukin-1 beta "IL-1ß" in renal tissue was detected using immunohistochemistry. RESULTS: Hypertonic glycerol administration led to severe renal tubular damage with a significant elevation of blood urea nitrogen, serum creatinine, creatinine kinase, CK MB and myoglobin levels and overexpression of IL-1ß compared to control group. Valproic acid administration attenuated both the muscle injury and the acute kidney injury induced by hypertonic glycerol, estimated through a significant reduction of creatinine kinase, myoglobin, and serum creatinine. Valproic acid administration caused a significant increase in GSH in the hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group. A significant decrease in tubular necrosis grade, and expression of IL-1ß in hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group was observed. CONCLUSION: This study demonstrates, for the first time to the best of our knowledge, that valproic acid could ameliorate the rhabdomyolysis and the related acute kidney injury in rats.

Protective effect of the standardized extract of ginkgo biloba (EGb761) against hypertension with hypercholesterolemia-induced renal injury in rats: Insights in the underlying mechanisms.

The potential protective role of the standardized leaf extract of ginkgo biloba (EGb761) on hypertension with hypercholesterolemia-induced renal injury was investigated in rats. Hypertension was induced by L-N(G)-nitroarginine methyl ester (L-NAME) and hypercholesterolemia was induced by feeding rats with a diet containing 1% cholesterol. In these animals repeated treatment with EGb761 produced a progressive reduction in the systolic, diastolic and mean arterial blood pressure (BP). EGb761 increased the progressive reduction in the systolic, diastolic and mean arterial BP induced by repeated administration of losartan with simvastatin. EGb761 corrected the compromised serum lipid profile and enhanced the effect of losartan with simvastatin on lipid profile. EGb761 protected against hypertension with hypercholesterolemia-induced renal injury as assessed by measurement of serum renal function markers and by histopathological examination. EGb761 enhanced the renoprotective effect of losartan with simvastatin in these rats. Concomitantly, hypertension with hypercholesterolemia-induced elevation of renal tissue malondialdehyde (MDA) and nitrite levels and reduction of intracellular reduced glutathione (GSH) level were inhibited by repeated treatment with EGb761. In addition, hypertension with hypercholesterolemia-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels in renal tissues were inhibited by treatment with EGb761. Also, EGb761 inhibited hypertension with hypercholesterolemia-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1ß in the kidney tissues. Losartan with simvastatin produced similar effects on renal tissues oxidative stress, nitrite and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1ß. EGb761 enhanced losartan with simvastatin effects. These results indicate that EGb761 has the ability to protect against hypertension with hypercholesterolemia-induced renal injury. The ability of EGb761 to provide this renoprotective effect may positively correlate, besides its antihypertensive and antihypercholesterolemic effects, to its ability to suppress renal oxidative stress, nitrosative stress and inflammation.