Morin attenuates sepsis-induced acute kidney injury by regulating inflammatory responses, oxidative stress and tubular regeneration (morin and sepsis-induced acute kidney injury).

Sepsis-associated acute kidney injury (AKI) is a health complication, encompassing excessive inflammatory response, oxidative stress, and tubular necrosis; leading to kidney failure and death. Sepsis treatments are nonspecific and palliative. In this study, we evaluated the effect of morin, a flavonoid with known nephroprotective capabilities, on sepsis-induced AKI by dividing eighty male mice into: normal, morin-treated, septic, and septic mice treated with morin. Half of the groups were sacrified 3 days post sepsis induction, while the rest was sacrified on the 7th day. Treating septic mice with morin resulted in the amelioration of sepsis-associated pathophysiological renal alterations and the increase of the survival and recovery rates compared with those of septic control group. These findings indicate that morin has a therapeutic effect against sepsis-associated AKI via its anti-inflammatory, antioxidant and regenerative effects. Thus, it could be used as potential pharmacological intervention for preventing renal complications of sepsis.

Flaxseed lignans alleviates isoproterenol-induced cardiac hypertrophy by regulating myocardial remodeling and oxidative stress.

Cardiovascular diseases, the leading global cause of death, are usually associated with cardiac hypertrophy (CH). CH is an adaptive response of the heart against cardiac overloading, but continuous CH accelerates cardiac remodeling and results in heart failure. Available CH therapies delay the progress of heart failure, but they often fail to control symptoms or restore quality of life. Although flaxseed lignans have been shown to have significant anti-oxidant, anti-hypertensive, anti-inflammatory, and anti-fibrotic effects in various cardiovascular diseases, little is known about their effect on CH. Thus, this study evaluated the therapeutic effect of flaxseed lignans on CH, which was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Flaxseed lignans (200 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological, and ultrastructural analyses were performed. Flaxseed lignans significantly ameliorated CH structural and functional alterations as shown by echocardiography. Lignans also reduced the relative heart weight, significantly decreased the elevated CK-MB and the lipid peroxidation marker malondialdehyde, augmented the myocardial total antioxidant capacity, and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The results demonstrate promising anti-hypertrophic effect of flaxseed lignans against isoproterenol-induced cardiac hypertrophy, via regulating myocardial remodeling and oxidative stress. Therefore, lignans could be used as potential pharmacological intervention in the management of CH.

Calanus oil attenuates isoproterenol-induced cardiac hypertrophy by regulating myocardial remodeling and oxidative stress.

Calanus oil, an oil extracted from the marine crustacean Calanus finmarchicus, is one of the richest sources of omega-3 and poly-unsaturated fatty acids. Although calanus oil has been shown to have a significant anti-hypertensive, anti-inflammatory, anti-fibrotic and anti-obesity effects in various cardiovascular diseases, but little is known about its effect on pathological cardiac hypertrophy. Thus, the present study was carried out to evaluate the therapeutic effect of calanus oil on cardiac hypertrophy. Cardiac hypertrophy was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Calanus oil (400 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological and ultrastructural analyses were performed. Calanus oil treatment significantly ameliorated isoproterenol-induced structural and functional alterations in echocardiography. Calanus oil also reduced the relative heart weight, significantly decreased the elevated cardiac enzymes (LDH and CK-MB) and the lipid peroxidation marker (MDA), augmented the myocardial antioxidant status (TAC), and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The present study, for the first time, provided morphometric, biochemical, histological and ultrastructural evidences supporting the promising anti-hypertrophic effect of calanus oil against ISO-induced cardiac hypertrophy. This anti-hypertrophic effect of calanus oil is via regulating myocardial remodeling and oxidative stress. Therefore, it could be used as potential pharmacological intervention in the management of cardiac hypertrophy.

Spirulina inhibits hepatocellular carcinoma through activating p53 and apoptosis and suppressing oxidative stress and angiogenesis.

BACKGROUND: Most hepatocellular carcinoma cases are diagnosed at late stages of the disease, which makes it the second cause of cancer mortality worldwide. For advanced-stage patients, chemotherapeutic drugs are the best treatment option; however, their adverse effects and high cost are still major obstacles for effective treatment. Spirulina microalga is a rich source of nutritional and bioactive elements and potential pharmaceuticals, which has an -proliferative effect against several cancer cell lines. It also has a prophylactic effect against the early stages of some cancer models, including hepatocellular carcinoma. AIMS: The present study was carried out to evaluate the therapeutic anticarcinogenic effect of spirulina against advanced murine hepatocellular carcinoma. MAIN METHODS: Hepatocarcinoma was induced by a single injection of diethylnitrosamine (100 mg/kg, intraperitoneally) followed by 22 weekly injections of carbon-tetrachloride (0.5 mg/kg, i.p). Spirulina (250 and 500 mg/kg bw) was given orally, from week 25 to 28, after the establishment of hepatocellular carcinoma. KEY FINDINGS: Spirulina inhibited HCC structural and functional alterations, manifested by improving the survival rate, significantly decreasing the tumor marker AFP, and the count and size of the hepatic nodules, as well as downstaging HCC. This was accompanied with the augmentation of the endogenous antioxidant capacity, apoptosis (Bax) and the tumor suppressor protein (p53), as well as the suppression of tissue levels of the lipid peroxidation marker (MDA) and neoangiogenesis marker (VEGF). SIGNIFICANCE: In conclusion, spirulina has an anticarcinogenic effect against advanced hepatocellular carcinoma exerted through activating the tumor suppressor protein p53 and apoptosis, and suppressing oxidative stress and angiogenesis.

Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation.

Aspirin is a commonly prescribed non steroidal anti-inflammatory drug, but its prolonged use injures the gastric mucosa. The present study was carried out to evaluate the ameliorative effect of spirulina against aspirin-induced gastric ulcer in albino mice. Gastric ulcer was induced by oral administration of aspirin (500 mg/kg bw). Spirulina (250 and 500 mg/kg bw) was given orally for 3 days after the induction of gastric ulcer. Spirulina ameliorated aspirin-induced gastric ulcer by improving the gross morphology, histology and mucous layer of gastric tissue, augmenting the endogenous enzymatic and non-enzymatic antioxidants (reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase) and the cytoprotective marker (COX-1), and by alleviating tissue levels of the lipid peroxidation marker (malondialdehyde) and inflammatory mediators (TNF-α, COX-2 and NO). In conclusion, spirulina has a therapeutic potential in aspirin-induced gastric injury by alleviating oxidative stress and inflammation.

Effect of dehydroepiandrosterone on the liver of perimenopausal rat: multiple doses study.

Dehydroepiandrosterone (DHEA) is a widespread nutritional "anti-aging" supplement. Exogenous supplementation of DHEA is now being commonly used to augment ovarian stimulation in perimenopausal women with diminished ovarian reserve. Whether DHEA causes side effects in such age is, however, unknown. Thus, this study investigates the effects of pharmacological doses of DHEA supplementation on the liver of perimenopausal rats. DHEA supplementation to perimenopausal rats resulted in slight hepatomegaly and steatosis, hepatocytic hypertrophy, mitochondrial swelling, elevation in serum alanine aminotransaminase levels, in addition to the accumulation of lipid droplets and lipolysosomes in a dose-dependent manner. In conclusion, long-term administration of high doses of DHEA causes ultrastructural alterations and changes in the levels of cholesterol and triglyceride in hepatocytes of perimenopausal rats. DHEA at a dose of 50 mg/kg improves health and decreases the body weight, with the least side effects on the liver of perimenopausal rats.

Epididymal ultrastructural changes associated with chronic cholestasis after bile duct ligation in adult rats.

Testicular atrophy and testesterone insufficiency have been commonly reported associated with chronic liver diseases. Though testosterone dependent, the epididymal changes induced by liver disease have never been studied before. Thus, this study aimed to assess the ultrastructural events in the epididymis of rats with chronic obstructive jaundice. Chronic cholestasis induced many epididymal structural alterations manifested by the reduced tubular diameters, thickening of the tubular basement membrane, and regression of the principal cells. This was accompanied with reduction of principal cell organelles, cytoplasmic vacuolations, nuclear alterations, and stereovilli loss. The results establish that chronic cholestasis causes epididymal structural changes due to androgen deficiency.

Effects of dehydroepiandrosterone on the ovarian reserve and pregnancy outcomes in perimenopausal rats (DHEA and fertility in perimenopausal rats).

BACKGROUND: Dehydroepiandrosterone (DHEA) is a weak androgen and a crucial precursor of sex steroids. Exogenous supplementation of DHEA is now being commonly used to augment ovarian stimulation in women with diminished ovarian reserve. However, the effects of DHEA are controversial. AIMS: This study verifies the effects of pharmacologic doses of DHEA on the ovarian reserve variables, follicular development, reproductive function, and pregnancy outcomes of perimenopausal rats. MAIN METHODS: The reproductive function was studied by monitoring the estrous cycle and hormones. The ovarian reserve was studied by testing the anti-mullerian hormone and ovarian histology. The follicular development was studied histologically and immunohistochemically. KEY FINDINGS: DHEA supplementation at a dose of at 50 mg/kg improved the ovarian reserve and pregnancy outcomes. Higher doses of DHEA caused PCOs-like symptoms manifested by the development of cystic follicles and low ovarian reserve and pregnancy outcomes. SIGNIFICANCE: DHEA is a promising treatment that improves the ovarian reserve parameters and pregnancy outcomes. Further studies are needed to determine the optimal dose and duration.

Chronic cholestasis is associated with hypogonadism and premature ovarian failure in adult rats (cholestasis causes ovarian hypogonadism).

Hypogonadism is a well-known complication in males with chronic liver diseases. However, the consequences of chronic hepatopathies on female reproductive capacities have received relatively little attention. The present study evaluates the effect of chronic obstructive jaundice on the ovary of adult cycling rats. Estrous cyclicity was monitored to check the functional status of the hypothalamic-pituitary-ovarian axis. Ovarian changes were assessed using histomorphometric, immunohistochemical, and ultrastructural techniques. Chronic cholestasis was associated with estrous cycle irregularities, diminished ovarian weight, primordial follicle loss, atretic follicle prevalence, marked stromal fibrosis, and diminished immunoexpression of proliferation marker and estrogen receptors, in addition to many ultrastructural alterations in theca, granulosa cells, and oocytes of antral follicles. The results establish that chronic cholestasis causes hypogonadism and premature ovarian insufficiency in adult cycling female rats.

Kiwi fruit (Actinidia deliciosa) ameliorates gentamicin-induced nephrotoxicity in albino mice via the activation of Nrf2 and the inhibition of NF-κB (Kiwi & gentamicin-induced nephrotoxicity).

Gentamicin is a potent aminoglycoside antibiotic, but the risk of nephrotoxicity limits its prolonged use. The toxicity of gentamicin is believed to result from oxidative stress, a condition that could be counteracted by dietary antioxidants. This study determines the possible renoprotective effects of kiwifruit against the pathophysiological and ultrastructural alterations induced by gentamicin. Mice were intraperitoneally injected with gentamicin (100mg/kg body weight) for eight consecutive days, and kiwi juice was administered for 8days, either concomitant to or after gentamicin injection. Gentamicin caused nephrotoxicity evidenced by the significant elevation of serum creatinine and blood urea nitrogen levels, along with significant reduction of serum sodium and potassium ions, compared to normal controls. This was associated with proximal tubular necrosis, lysosomal accumulation and mitochondrial alterations, together with glomerular atrophy, mesangial hypercellularity, and inflammatory cell infiltration. Moreover, immunohistochemical results pointed to the relevant role of Nrf2 and NF-κB in gentamicin-induced nephrotoxicity. Kiwi administration, especially when given after gentamicin injection, significantly ameliorated gentamicin-induced pathophysiological alterations, increased the nuclear immunoreactivity of Nrf2 and decreased that of NF-κB. In short, kiwi fruit shows a promising role as a nephroprotective agent against gentamicin-induced nephrotoxicity via attenuating oxidative stress, inflammation and cell death.

Role of nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver: Nicotinamide effect in acetaminophen-damged liver.

Acetaminophen is a widely used analgesic and antipyretic agent, which is safe at therapeutic doses. However, overdoses of acetaminophen induce severe oxidative stress, which leads to acute liver failure. Nicotinamide has proven effective in ameliorating many pathological conditions that occur due to oxidative stress. This study verifies the prophylactic and therapeutic effects of nicotinamide against the hepatic pathophysiological and ultrastructural alterations induced by acetaminophen. Wistar rats intoxicated with an acute overdose of acetaminophen (5g/kg b.wt) were given a single dose of nicotinamide (500mg/kg b.wt) either before or after intoxication. Acetaminophen caused significant elevation in the liver functions and lipid peroxidation marker, and decline in the activities of the hepatic antioxidant enzymes. This oxidative injury was associated with hepatic centrilobular necrosis, hemorrage, vacuolar degeneration, lipid accumulation and mitochondrial alterations. Treating intoxicated rats with nicotinamide (500mg/kg) significantly ameliorated acetaminophen-induced biochemical changes and pathological injuries. However, administering the same dose of nicotinamide to healthy animals or prior to acetaminophen-intoxication induced hepatotoxicity. Caution should be taken when administering high doses of NAM because of its possible hepatotoxicity. Considering the wide use of nicotinamide, there is an important need for monitoring nicotinamide tolerance, safety and efficacy in healthy and diseased subjects.

Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid.

AIMS: Testicular atrophy has been commonly reported in patients with chronic liver diseases. Ursodeoxycholic acid is the most widely used drug for the treatment of many liver diseases. However, its effect on testicular ultrastructure associated with chronic cholestasis has never been studied. Thus, this study aimed to assess how chronic obstructive jaundice affects the testicular ultrastructure and whether it affects the androgen receptor or the proliferating cell nuclear antigen. The role of ursodeoxycholic acid was also investigated. MAIN METHODS: Cholestasis was induced by bile duct ligation. Samples were collected 4weeks postoperative. Testicular changes were assessed using immunohistochemistry and transmission electron microscopy. KEY FINDINGS: Chronic cholestasis resulted in testicular atrophy evidenced by shrinkage and deformation of seminiferous tubules, thickening of peritubular boundaries, vacuolation, disorganization of germ cells, and maturation arrest. This was accompanied by decreased immunoreactivity of androgen receptors and proliferating cell nuclear antigen. Administration of ursodeoxycholic acid improved the testicular morphology and reversed cholestasis-induced immunohistochemical and ultrastructural changes. SIGNIFICANCE: Ursodeoxycholic acid can improve the testicular ultrastructure and restore the spermatogenic process in rats with chronic cholestasis. These findings support the clinical application of ursodeoxycholic acid in cholestatic patients especially those with hypogonadism.

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats.

Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bile duct ligation. Bile duct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug.

Effects of garlic on Schistosoma mansoni harbored in albino mice: molecular characterization of the host and parasite.

Garlic has been used for its health benefits for thousands of years. Modern research confirmed many of the healing properties of garlic, including its antiparasitic activity. This study was designed to evaluate the antischistosomal action of garlic through detecting the changes in DNA profile of Schistosoma mansoni worms and the infected mouse. Forty mice were subcutaneously infected with ~200 Schistosoma mansoni cercariae/mouse. Infected mice were divided into four equal groups: non-treated, prophylactic, therapeutic, and continuously-treated. Non-infected control and garlic-treated groups were assigned for the sake of comparison. Garlic extract (50mg/kg bw/mouse) was given orally, day after day, at a fixed daytime. Seven weeks post-infection, adult schistosomes were recovered by perfusion and the livers of the mice were excised out and were processed for DNA extraction and Random Amplification of Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR). The results showed that garlic exerted no major changes in the genome of schistosomes. Nevertheless, that schistosomal infection induced genetic alterations in the DNA of mice, and garlic was able to ameliorate such alterations to a great extent.