ABSTRACT
The protective effect of eugenol and its possible mechanisms were investigated in rats with acute doxorubicin cardiotoxicity. Cardiac toxicity was induced by a single intraperitoneal injection of doxorubicin (20 mg/kg). Eugenol treatment (5 mg/kg/day, orally) was started 2 days before doxorubicin administration and continued for five consecutive days. Eugenol significantly reduced the elevated serum creatine kinase and lactate dehydrogenase levels, and restored the electrocardiographic disturbances resulted from doxorubicin administration. Also, eugenol reversed doxorubicin-induced deficits in the antioxidant defense mechanisms, decreased lipid peroxidation and attenuated the elevations in cytosolic Ca(2+) and nitric oxide levels in cardiac tissue. In addition, doxorubicin-induced cardiac tissue damage observed by histopathological examination was markedly ameliorated with eugenol. Immunohistochemical analysis revealed that eugenol prevented the doxorubicin-induced activation of caspase-3 in cardiomyocytes. The cardioprotective effect afforded by eugenol was not significantly inhibited by prior administration of capsazepine, the transient potential vanilloid receptor-1 antagonist. It was concluded that eugenol, through its antioxidant activity and its ability to reduce cardiac Ca(2+) accumulation and nitric oxide levels, is a potential candidate to protect against acute doxorubicin cardiotoxicity, a major and dose-limiting clinical problem.
Subject(s)
Antibiotics, Antineoplastic/toxicity , Cardiotonic Agents/therapeutic use , Cardiotoxins/toxicity , Doxorubicin/toxicity , Eugenol/therapeutic use , Heart Failure/prevention & control , Heart/drug effects , Animals , Antioxidants/therapeutic use , Calcium Signaling/drug effects , Capsaicin/analogs & derivatives , Capsaicin/pharmacology , Caspase 3/metabolism , Heart Failure/chemically induced , Heart Failure/metabolism , Heart Failure/pathology , Lipid Peroxidation/drug effects , Male , Myocardium/metabolism , Myocardium/pathology , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , TRPV Cation Channels/antagonists & inhibitorsABSTRACT
The protective effect of coenzyme Q10 against testicular toxicity induced by sodium arsenite (10mg/kg/day, orally for two consecutive days) was investigated in rats. Coenzyme Q10 treatment (10mg/kg/day, i.p.) was applied for five consecutive days, starting three days before arsenite administration. Coenzyme Q10 significantly increased serum testosterone level which was reduced by sodium arsenite. Coenzyme Q10 significantly suppressed lipid peroxidation, restored the depleted antioxidant defenses, and attenuated the increases of tumor necrosis factor-α and nitric oxide resulted from arsenic administration. Also, the elevation of arsenic ion, and the reductions of selenium and zinc ions in testicular tissue were mitigated by coenzyme Q10. Histopathological examination showed that testicular injury mediated by arsenic was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the arsenic-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3 in testicular tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of arsenic intoxication.
Subject(s)
Arsenites/toxicity , Sodium Compounds/toxicity , Testis/drug effects , Testis/injuries , Ubiquinone/analogs & derivatives , Animals , Arsenic/metabolism , Immunohistochemistry , Male , Rats , Rats, Sprague-Dawley , Selenium/metabolism , Testis/metabolism , Testis/pathology , Testosterone/blood , Ubiquinone/pharmacology , Zinc/metabolismABSTRACT
The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-alpha, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-kappaB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.
Subject(s)
Acute Kidney Injury/chemically induced , Cisplatin/adverse effects , Kidney/drug effects , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Antioxidants/pharmacology , Blood Urea Nitrogen , Caspase 3/metabolism , Cisplatin/metabolism , Cisplatin/pharmacology , Creatinine/blood , Creatinine/metabolism , Creatinine/pharmacology , Glutathione/adverse effects , Glutathione/metabolism , Glutathione/pharmacology , Lipid Peroxidation/drug effects , Male , Mice , Nitric Oxide/adverse effects , Nitric Oxide/metabolism , Nitric Oxide/pharmacology , Tumor Necrosis Factor-alpha/adverse effects , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Ubiquinone/adverse effects , Ubiquinone/analogs & derivatives , Ubiquinone/metabolism , Ubiquinone/pharmacology , Urea/blood , Urea/metabolism , Urea/pharmacologyABSTRACT
The protective effects of telmisartan, the angiotensin II-receptor antagonist, were investigated in rats with type 2 diabetes mellitus exposed to acute gastric ulceration. Following successful induction of diabetes, telmisartan treatment (1 mg/kg/day, orally) was started and continued for 8 weeks, after which acute gastric ulceration was induced by indomethacin. Telmisartan significantly attenuated the hyperglycemia and hypoinsulinemia in diabetic rats. Also, telmisartan significantly reduced the elevations of total gastric acid output, pepsin activity, gastric ulcer index and gastric mucosal tumor necrosis factor-alpha, nitric oxide, malondialdehyde and caspase-3 activity, and restored the depleted antioxidant defenses (reduced glutathione level, and superoxide dismutase and catalase activities) caused by indomethacin administration in diabetic rats. Histopathological gastric tissue damage induced by indomethacin in diabetic rats was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan markedly attenuated the reduction in insulin content of pancreatic islet beta-cells, and prevented the indomethacin-induced overexpression of inducible nitric oxide synthase and nuclear factor-kappaB in gastric mucosa of diabetic rats. It was concluded that telmisartan represents a potential therapeutic option to reduce the risk of gastric ulceration induced by nonsteroidal anti-inflammatory drugs in type 2 diabetic patients.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Indomethacin , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Animals , Antioxidants/metabolism , Blood Glucose/metabolism , Caspase 3/metabolism , Gastric Acid/metabolism , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Immunohistochemistry , Insulin/metabolism , Male , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Rats , Rats, Sprague-Dawley , Stomach Ulcer/complications , Stomach Ulcer/metabolism , Telmisartan , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder characterized by hydranencephaly; brain stem, basal ganglia, and spinal cord diffuse clastic ischemic lesions with calcifications; glomeruloid vasculopathy of the central nervous system and retinal vessels; and a fetal akinesia deformation sequence (FADS) with muscular neurogenic atrophy. To identify the molecular basis for Fowler syndrome, we performed autozygosity mapping studies in three consanguineous families. The results of SNP microarrays and microsatellite marker genotyping demonstrated linkage to chromosome 14q24.3. Direct sequencing of candidate genes within the target interval revealed five different germline mutations in FLVCR2 in five families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis. This is the first gene to be associated with Fowler syndrome, and this finding provides a basis for further studies to elucidate the pathogenetic mechanisms and phenotypic spectrum of associated disorders.
Subject(s)
Germ-Line Mutation , Hydranencephaly/genetics , Hydrocephalus/genetics , Membrane Transport Proteins/genetics , Receptors, Virus/genetics , Vascular Diseases/genetics , Abnormalities, Multiple/genetics , Amino Acid Sequence , Amino Acid Substitution , Animals , Base Sequence , Chromosomes, Human, Pair 14/genetics , Consanguinity , Conserved Sequence , DNA/genetics , Female , Genes, Recessive , Humans , Male , Mice , Models, Molecular , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Pedigree , Phenotype , Polymorphism, Single Nucleotide , Pregnancy , Protein Structure, Tertiary , Sequence Homology, Amino Acid , SyndromeABSTRACT
We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-alpha and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-alpha, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , Kidney Diseases/drug therapy , Kidney/drug effects , Reperfusion Injury/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Blood Pressure/drug effects , Blood Urea Nitrogen , Caspase 3/metabolism , Catalase/metabolism , Creatinine/blood , Disease Models, Animal , Glutathione/metabolism , Homocysteine/blood , Kidney/blood supply , Kidney/metabolism , Kidney/ultrastructure , Kidney Diseases/metabolism , Kidney Diseases/pathology , Kidney Diseases/physiopathology , Male , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Superoxide Dismutase/metabolism , Telmisartan , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The hepatoprotective effect of carnosine was investigated against cadmium-induced acute liver injury in mice. Hepatotoxicity was induced by a single i.p. injection of cadmium chloride (6.5mg/kg). Carnosine treatment (10mg/kg/day, i.p.) was applied for three consecutive days, starting one day before cadmium administration. Carnosine significantly decreased the cadmium-induced elevations in serum aminotransferases. Carnosine suppressed lipid peroxidation and restored the deficits in the antioxidant defense mechanisms (reduced glutathione level, and catalase and superoxide dismutase activities) in liver tissue resulted from cadmium administration. Also, the reductions in hepatic nitric oxide and zinc ion levels, and the increases in hepatic cadmium ion concentration, and myeloperoxidase and caspase-3 activities following cadmium exposure were significantly attenuated by carnosine treatment. In addition, carnosine markedly ameliorated cadmium-induced liver tissue damage as evidenced by light and electron microscopic examinations. It was concluded that carnosine can be considered a potential candidate to protect the liver against the deleterious effect of acute cadmium intoxication.
Subject(s)
Cadmium/toxicity , Carnosine/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Liver/drug effects , Liver/pathology , Male , MiceABSTRACT
The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2mg/kg). Hemin was given for three consecutive days (40 micromol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-alpha and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium.
Subject(s)
Cadmium Poisoning/pathology , Cadmium Poisoning/prevention & control , Hemin/therapeutic use , Testicular Diseases/chemically induced , Testicular Diseases/prevention & control , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Caspases/metabolism , Enzyme Inhibitors/pharmacology , Glutathione/metabolism , Heme Oxygenase-1/antagonists & inhibitors , Male , Malondialdehyde/metabolism , Microscopy, Electron , Nitric Oxide/metabolism , Oxidants/metabolism , Protoporphyrins/pharmacology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Testicular Diseases/pathology , Testis/pathology , Testis/ultrastructure , Testosterone/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The therapeutic potential of hemin, the heme oxygenase-1 inducer, was investigated against renal damage induced by acute acetaminophen overdose in rats. Nephrotoxicity was induced by a single oral dose of acetaminophen (2.5g/kg). Hemin was given as a single s.c. injection (40µmol/kg), 1h following acetaminophen administration. Hemin treatment restored blood urea nitrogen and serum creatinine levels that were elevated by acetaminophen. Hemin also compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in renal tissue resulted from acetaminophen administration. Hemin attenuated the acetaminophen-induced elevations in renal tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated acetaminophen-induced renal damage observed by light microscopic examination. The therapeutic effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin represents a potential therapeutic option to protect renal tissue from the detrimental effects of acute acetaminophen overdose.
ABSTRACT
BACKGROUND: Holoprosencephaly (HPE) is a rare and serious brain anomaly of heterogeneous aetiology. AIMS: description of neuropathologic patterns of HPE to eventually integrate it into recognized syndrome METHODS: The authors report 15 cases of HPE, examined at the department of pathology of Sousse (Tunisia) over a period of 11 years. RESULTS: The average age of mothers was 32 years and 46% of them were primigestes. The rate of consanguinity was 45%. The population of the study was formed of 13 foeti, 12 of which arose from a medical interruption of pregnancy, and 2 newborns. The average foetal age was of 25,5 weeks of gestation. Antenatal diagnosis was performed on ultrasounds signs represented by a hydrocephalus (7 cases), a microcephaly (4 cases), a harmonious delay of growth (3cas) and a facial dysmorphy (38%) dominated by cyclopia. Neuropathologic Exam identified 13 cases of alobair HPE and 2 cases semi lobar. The HPE was isolated in 2 cases with an unknown caryotype, it was syndromic in 13 cases, associated with a chromosome abnormality confirmed in 3 observations. CONCLUSION: The neonatal outcome of this deformation remains very poor justifying the interruption of pregnancy except in the lobar forms. An exhaustive domestic inquiry is compulsory to propose to parents a most adequate genetic counselling.
Subject(s)
Fetus/pathology , Holoprosencephaly/pathology , Adult , Female , Humans , Retrospective Studies , Young AdultABSTRACT
Our retrospective study was performed on 10 cases of granulomatous mastitis registered in Obstetric Gynaecology Department and Pathology Department of CHU F. Hached, Sousse, during 8 years period. The mean age was 36.4 years (range 32-59). Among these 10 cases. 8 were observed in reproductive-age women and 2 were noted in menopausal women. Clinical findings showed unilateral breast nodule associated with inflammatory signs in 4 cases, mammelonary retraction in 2 cases and serous or sero-purulent mamelonnary flow in 4 cases. Mamnmographic examination suggested a malignant tumor in 5 patients. In all cases, the diagnosis is made by histopathology. Surgical treatment consisted in wide excision with drainage or radical mastectomy, eventually with combination with antibiotic therapy and non steroid anti-inflammatory drugs. Prognostic features showed a good cicatrization in 4 cases, local recurrence and cutaneous fistulization in one patient. Granulomatous mastitis aetiology is still unclear, auto-immune aetio-pathogenesis appears more interesting and should be clarified.
Subject(s)
Mastitis , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Breast/pathology , Diagnosis, Differential , Drainage , Female , Humans , Mammography , Mastectomy, Radical , Mastitis/diagnosis , Mastitis/diagnostic imaging , Mastitis/pathology , Mastitis/surgery , Middle Aged , Prognosis , Recurrence , Retrospective StudiesABSTRACT
A case of primary myxoid leiomyosarcoma of the ovary in a 50-year-old Tunisian woman is presented. Bilateral salpingooophorectomy and hysterectomy were carried out without any adjuvant therapy. The tumour were investigated histologically and immunohistochemically. Smooth-muscle actin and progesterone receptors was strongly demonstrated in neoplastic cells, bcl-2 was weakly and diffusely demonstrated. Relevant literature is reviewed based on the histologic and immunohistochemical features with emphasis on diagnosis and therapeutic problems and prognosis indicators.