Ashraf M. Abdel-Moneim

Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage

The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.

Prophylactic and therapeutic effects of taurine against aluminum-induced acute hepatotoxicity in mice

Aluminum is a well known neurotoxin and a possible candidate of hepatotoxins to humans. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. In the present study, Aluminum (AlCl(3)) intoxication (a single injection of 25mg Al(3+)/kg, i.p.) for 24h in mice resulted in elevations in serum alanine aminotransferase activity and serum tumor necrosis factor and hepatic malondialdehyde levels. Aluminum reduced the activities of glutathione peroxidase, glutathione S-transferase, quinone oxidoreductase, and catalase in liver. In addition, Al caused hepatic hemorrhage, cellular degeneration as well as necrosis of hepatocytes. Ultrastructure examination showed swelling of mitochondria, derangement of rough endoplasmic reticulum cisternae and pleomorphic nuclei with abnormal chromatin distribution. Taurine, a sulfur-containing amino acid was administered to mice daily for 5 days before (at 100mg/kg, i.p.) or 2h after (a single dose of 1g/kg, i.p.) aluminum administration. Treating mice with taurine at either dosing regimens, pre- or post-aluminum administration alleviated aluminum oxidative damaging effects. The rate of recovery was better when taurine was administered prior to Al. Taurine had anaphylactic and therapeutic activity against hepatotoxicity induced by aluminum in mice.

Hemin attenuates cisplatin-induced acute renal injury in male rats.

Background. The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. Methods. The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. Results. A single intraperitoneal dose of CP (10u2009mg/kgu2009b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40u2009µmol/kgu2009b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. Conclusion. The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.

The influence of taurine pretreatment on aluminum chloride induced nephrotoxicity in Swiss albino mice

The present study was carried out to investigate (1) the alterations in biochemical parameters, free radicals and enzyme activities induced by aluminum chloride (AlCl₃) in kidney of male Swiss albino mice, and (2) the role of taurine in alleviating the nephrotoxic effects of AlCl₃. Taurine plays an important role as an antioxidant and is consequently expected to protect tissues from damage caused by reactive oxygen metabolites.The animals were randomized into four groups (n=6/group). Group I was the control group. Group II received a single dose of AlCl₃ (25 mg Al³⁺/kg b.w, ip). Group III received taurine (100 mg/kg b.w., ip) for 5 consecutive days before administration of AlCl₃ (25 mg Al³⁺/kg b.w, ip). Group IV received taurine (100 mg/kg b.w., ip) for 5 consecutive days. 24 h following the administration of compounds, all the mice were assessed using serum and tissue homogenate biomarkers as well as the pathological evaluation. Exposure to AlCl₃ led to an increased level of renal lipid peroxidation as measured by malondialdehyde (MDA), while reduced glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) decreased. Marked elevation of blood urea and serum creatinine concentrations were also observed in AlCl₃ treated mice, thereby indicating renal damage. All these factors were significantly improved by taurine pretreatment. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of taurine. Thus these results may indicate that taurine treatment protects against functional, biochemical and morphological damage in AlCl₃-induced acute renal failure in mice.

Biochemical and histopathological changes in liver of the Nile tilapia from Egyptian polluted lakes

The aim of the present study was to analyze the impact of environmental contamination on oxidative stress and histopathologic biomarkers in liver of the Nile tilapia, Oreochromis niloticus, collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut as well as Boughaz El-Maadiya, a channel in Lake Edku. The SEB was the less-impacted site, and thus considered as a reference. High concentrations of heavy metals (cadmium, copper, iron, lead, zinc, and manganese) were detected in fish liver at sites with anthropogenic pressure. All biomarkers, lipid peroxidation (in the MB, NWB, and Lake Edku), superoxide dismutase (in the MB and NWB), and glutathione peroxidase, and reduced glutathione (in the NWB) were found to be significantly higher compared to the reference values. Catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed a varied response and displayed significantly lower activities in the polluted sites. Certain hepatic lesions, detected microscopically, were stimulated in fish from the MB and NWB, reflecting the high contamination of these areas. These included foci of necrosis, melanomacrophage infiltration, congestion, nuclear pyknosis, and extensive vacuolation corresponding to relatively higher lipid content. Overall, our results suggest that the selected biomarkers are useful for the assessment of pollution impacts in natural aquatic environments influenced by multiple pollution sources. The existence of chronic background pollution of the test sites implies that the observed biomarker responses cannot be solely attributed to heavy metals.

N-acetylcysteine and meso-2,3 dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats

Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

Curcumin Ameliorates Lead (Pb 2+ )-Induced Hemato-Biochemical Alterations and Renal Oxidative Damage in a Rat Model

This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb2+ (25xa0mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30xa0mg of Curc/kg b.w., twice a day) for 7xa0days. Exposure of rats to Pb2+ caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb2+-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb2+ group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb2+. Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb2+ produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb2+-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb2+-induced toxicity.

Effects of Taurine against Histomorphological and Ultrastructural Changes in the Testes of Mice Exposed to Aluminium Chloride

Abstract The aim of this study was to investigate the protective effects of taurine against histomorphological and ultrastructural changes in the testes of Swiss albino mice caused by acute in vivo exposure to AlCl3. Light microscopy revealed that a single intraperitoneal (i.p.) dose of AlCl3 (25 mg kg-1 Al3+) was associated with sloughing, tubular atrophy, germ-cell degeneration, and foci of Leydig cell hyperplasia. In addition, transmission electron microscopy showed a destruction of inter-Sertoli cell tight junctions, apoptotic cell death of spermatogonia and primary spermatocytes, various types of abnormalities in spermatid morphology, accumulation of lipid droplets, reduction of the smooth endoplasmic reticulum (sER), and mitochondrial damage in Leydig cells. Taurine post-treatment at i.p. dose of 1 g kg-1 diminished these changes and significantly reduced the number of affected tubules compared to Al-poisoned mice. This is the first study to evidence that taurine protects against pathological changes in the testicular tissue of Al-treated mice. Sažetak DJELOVANJE TAURINA PROTIV HISTOMORFOLOŠKIH I ULTRASTRUKTURNIH PROMJENA U TESTISIMA MIŠEVA IZLOŽENIH ALUMINIJEVU KLORIDU Cilj je ovog istraživanja bio proučiti zaštitno djelovanje taurina od histomorfoloških i ultrastrukturnih promjena u testisima švicarskih albino miševa akutno izloženih AlCl3. Svjetlosnom je mikroskopijom utvrđena povezanost između jednokratne intraperitonealne (i.p.) doze AlCl3 (25 mg kg-1 Al3+) i odvajanja nekrotičnoga tkiva, atrofije tubula, degeneracije zametnih stanica te žarišta hiperplazije Leydigovih stanica. Usto su se elektronskom mikroskopijom mogli vidjeti razoreni čvrsti spojevi između Sertolijevih stanica, apoptoza spermatogonija i primarnih spermatocita, različite morfološke abnormalnosti spermatida, nakupljanje lipidnih kapi, stanjenje glatkog endoplazmatskog retikuluma (sER) te oštećenje mitohondrija u Leydigovim stanicama. Naknadna primjena taurina u i.p. dozi od 1 g kg-1 ublažila je ove promjene i značajno smanjila broj zahvaćenih tubula u odnosu na miševe otrovane aluminijem. Ovo je prvo istraživanje koje potvrđuje zaštitno djelovanje taurina protiv patoloških promjena na tkivu testisa miševa uzrokovanih aluminijem.

Gill Oxidative Stress and Histopathological Biomarkers of Pollution Impacts in Nile Tilapia from Lake Mariut and Lake Edku, Egypt

Various oxidative stress and histopathological biomarkers in gill tissues of Nile tilapia Oreochromis niloticus were investigated. Fish were collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut; and Boughaz El-Maadiya, a channel in Lake Edku. The oxidative stress biomarkers that were analyzed included lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), and glutathione redox cycle enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]). Levels of reduced glutathione (GSH) were also evaluated. Gill morphology was analyzed by light microscopy and scanning electron microscopy (SEM). Gill LPO was significantly higher in gill tissues of fish collected from the more heavily contaminated MB (40.0%) and NWB (51.4%) sites than in gill samples from the less-contaminated (reference) site, the SEB. Gill LPO in fish from Lake Edku was intermediate but was not significantly higher (17.1%) than the reference. The activities of antioxidant enzymes and the redox-sensitive thiol compound GSH were significantly lower in gill samples from the disturbed sites than in samples from the reference site. Specifically, SOD in MB, NWB, and Lake Edku samples; CAT and GPx in NWB samples; and GR activity and GSH content in MB and NWB samples were lower than those in SEB samples. In most cases, gill tissues from Lake Edku fish had intermediate levels of antioxidants. The main histopathological alterations observed in gills were epithelial lifting, hyperplasia and hypertrophy of the respiratory epithelium, lamellar fusion, and aneurysms. In addition, SEM results demonstrated transformation of the surface structure of epithelial pavement cells. Pathological reactions in the gills of Nile tilapia were most severe at the MB and NWB sites. Our findings suggest that Nile tilapia responded differently according to the environmental stress index in each sampling area. This study is the first to report gill oxidative stress and histopathologies in Nile tilapia from Egyptian aquatic environments.

Histopathological and ultrastructural perturbations in tilapia liver as potential indicators of pollution in Lake Al-Asfar, Saudi Arabia

Lake Al-Asfar (Al-Hassa, Saudi Arabia) is under threat from contaminants released through human activities such as agriculture and urban and industrial developments. In the present study, histopathologic and ultrastructural changes in liver of tilapia Oreochromis niloticus were analyzed to monitor the possible impact of pollution in Al-Asfar estuary. Heavy metals such as Ni, Fe, Zn, Co, Ba, Pb, and Cd were predominant in the lake water and far exceeded the international permissible limits. In fish samples, high prevalences of preneoplastic changes (50xa0%) and one case of cholangiocarcinoma were revealed in liver tissues. Cytological damage in fish hepatocytes included glycogen exhaustion, deformation of nuclear envelope, heterochromatin condensation, mitochondrial degeneration, vesiculation of rough endoplasmic reticulum, augmentation of smooth endoplasmic reticulum, and lysosomal proliferation. In conclusion, the observed biomarker responses were potential indicators of health impairment or disease in field fish populations, although there was no direct proof of a simple cause–effect relationship. This is the first biological effect assessment in Lake Al-Asfar using tilapia as suitable target species.