The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole- 5-carboxamide (1), that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4, respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5. The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6–11. The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, 1H-NMR, 13C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.

The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole- 5-carboxamide (1), that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4, respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5. The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6–11. The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, 1H-NMR, 13C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.

The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole- 5-carboxamide (1), that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4, respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5. The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6–11. The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, 1H-NMR, 13C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.

The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole- 5-carboxamide (1), that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4, respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5. The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6–11. The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, 1H-NMR, 13C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.

4-Nonylphenol (4-NP) is a nephrotoxic substance that is highly prevalent in aquatic environments. Nigella sativa seed (NSS) has many biological activities and is widely used throughout the world as a medicinal product. Therefore, in the present study, we investigated the cytoprotective effect of NSS on 4- NP-induced renal damage in African catfish (Clarias gariepinus). Thirty fish were divided into five equal groups: an untreated control group and four groups that were challenged with 4-NP at a dose of 0.1 mg L1 of aquarium water and fed a basal diet supplemented with 0%, 1%, 2.5%, and 5% NSS, respectively, for 3 weeks. Histological, histochemical, and ultrastructural features of the kidney were then assessed as biomarkers for renal tissue damage. Our results confirmed that 4-NP was a potent cytotoxic agent for the kidney tissue and induced renal damage, with 4-NP-intoxicated fish showing necrosis in the epithelial cells of the renal corpuscles, renal proximal convoluted tubules, and intertubular hematopoietic tissue, as well as loss of or a decrease in microvilli, a decrease in mitochondria, and an increase in the lysosomes in the epithelial cells of the proximal convoluted tubules. The kidneys of 4-NP-intoxicated fish also showed increased numbers of Perls’ Prussian blue-positive melanomacrophage centers and intraepithelial T-lymphocytes in the proximal convoluted tubules and plasma cells. The administration of NSS to 4-NP-challenged fish significantly minimized the cytotoxic effect of 4-NP, maintaining the normal kidney structure, with concentrations of 2.5% and 5% of feed being most effective for protecting the kidney against 4-NP-induced renal damage.

4-Nonylphenol (4-NP) is a nephrotoxic substance that is highly prevalent in aquatic environments. Nigella sativa seed (NSS) has many biological activities and is widely used throughout the world as a medicinal product. Therefore, in the present study, we investigated the cytoprotective effect of NSS on 4- NP-induced renal damage in African catfish (Clarias gariepinus). Thirty fish were divided into five equal groups: an untreated control group and four groups that were challenged with 4-NP at a dose of 0.1 mg L1 of aquarium water and fed a basal diet supplemented with 0%, 1%, 2.5%, and 5% NSS, respectively, for 3 weeks. Histological, histochemical, and ultrastructural features of the kidney were then assessed as biomarkers for renal tissue damage. Our results confirmed that 4-NP was a potent cytotoxic agent for the kidney tissue and induced renal damage, with 4-NP-intoxicated fish showing necrosis in the epithelial cells of the renal corpuscles, renal proximal convoluted tubules, and intertubular hematopoietic tissue, as well as loss of or a decrease in microvilli, a decrease in mitochondria, and an increase in the lysosomes in the epithelial cells of the proximal convoluted tubules. The kidneys of 4-NP-intoxicated fish also showed increased numbers of Perls’ Prussian blue-positive melanomacrophage centers and intraepithelial T-lymphocytes in the proximal convoluted tubules and plasma cells. The administration of NSS to 4-NP-challenged fish significantly minimized the cytotoxic effect of 4-NP, maintaining the normal kidney structure, with concentrations of 2.5% and 5% of feed being most effective for protecting the kidney against 4-NP-induced renal damage.

4-Nonylphenol (4-NP) is a nephrotoxic substance that is highly prevalent in aquatic environments. Nigella sativa seed (NSS) has many biological activities and is widely used throughout the world as a medicinal product. Therefore, in the present study, we investigated the cytoprotective effect of NSS on 4- NP-induced renal damage in African catfish (Clarias gariepinus). Thirty fish were divided into five equal groups: an untreated control group and four groups that were challenged with 4-NP at a dose of 0.1 mg L1 of aquarium water and fed a basal diet supplemented with 0%, 1%, 2.5%, and 5% NSS, respectively, for 3 weeks. Histological, histochemical, and ultrastructural features of the kidney were then assessed as biomarkers for renal tissue damage. Our results confirmed that 4-NP was a potent cytotoxic agent for the kidney tissue and induced renal damage, with 4-NP-intoxicated fish showing necrosis in the epithelial cells of the renal corpuscles, renal proximal convoluted tubules, and intertubular hematopoietic tissue, as well as loss of or a decrease in microvilli, a decrease in mitochondria, and an increase in the lysosomes in the epithelial cells of the proximal convoluted tubules. The kidneys of 4-NP-intoxicated fish also showed increased numbers of Perls’ Prussian blue-positive melanomacrophage centers and intraepithelial T-lymphocytes in the proximal convoluted tubules and plasma cells. The administration of NSS to 4-NP-challenged fish significantly minimized the cytotoxic effect of 4-NP, maintaining the normal kidney structure, with concentrations of 2.5% and 5% of feed being most effective for protecting the kidney against 4-NP-induced renal damage.

The current work intended to inspect the hepato-nephrotoxicity of gibberellic acid (GA3) in juvenile of Oreochromis niloticus as well as the possibility of restoration after dietary addition of different concentrations of Spirulina platensis (SP). Fishes were evenly assorted into five groups: Group I assigned as control, Group II fed on basal diet and exposed to 150 mg/L gibberellic acid (GA3). The 3rd, 4th, and 5th groups exposed to150 mg/L gibberellic acid (GA3) and previously fed for two months on SP supplemented diets at levels of 5, 20, and 100 g/ kg, respectively. Fish serum were utilized to check glucose, total protein, hepatic and renal functions, enzymatic and non-enzymatic antioxidants activities (superoxide dismautase; SOD, catalase; CAT, and total antioxidant capacity; TAC) as well as histopathological alterations in liver and kidney. The results showed that creatinine, uric acid, liver enzymes, glucose, total protein, SOD, and CAT were significantly elevated in GA3-treated group. Liver of GA3-treated fish manifested some histopathological changes (hypertrophy, cytoplasmic vacuolization, and apoptotic cells with pyknotic nuclei, necrosis, dilated blood sinusoids, and lymphocytic aggregation around the central veins). Kidney of GA3-exposed fish revealed edema of the epithelium lining of some renal tubules and some showed vacuolar degeneration and dissociation. Hypertrophy in the glomerulus was observed with dilated blood capillaries. SP supplementation restored these biochemical, antioxidants, and histological changes near to control levels. This improvement was higher with 100 g/kg SP showing concentration dependency. According to this study we can conclude that SP supplementation can improve the hepato- and nephrotoxicity caused by GA3 exposure indicating its role as potent antioxidant food additive.

Four hundred and fifty Nile tilapia (Oreochromis niloticus), each weighing ca. 4 g, were randomly allocated into five equal groups in triplicate. The first group acts as control (A0). A1, A2, A3 and A4 groups were fed on rations supplemented with diatom, Amphora coffeaeformis, at 2.5, 5.0, 7.5 and 10%, respectively, for 63 days. Assessment of fish growth, biochemical composition, erythrocyte alterations, gonadal maturation, serum biomarkers, and liver and intestinal pathogens was carried out to identify fish welfare. Fish were challenged by Aeromonas hydrophila injection for an additional 14 days; then, mortality rate and some blood parameters were monitored. Results demonstrated that Amphora sp. insignificantly impacted fish growth, but it induced significant depletion in lipid content. Blood smear investigation indicated erythrocyte alterations in A4 group compared with A0 group. Male gonadosomatic index and relative fecundity demonstrated an increment in A3 and A4 groups respectively. A boost in fish immunity of A3 group was demonstrated through serum biomarkers and pathogenic bacterial identification in liver and intestine compared with other groups. Cumulative mortality of stressed fish was 90% in the A0 group and decreased to 30% in the A3 group. Blood analysis of stressed fish indicated higher tolerance in the A3 group. In conclusion, Amphora sp. can be used as an immunostimulant for increasing disease resistance under stress conditions.

Recently, the oxidative stress and immunotoxicity biomarkers have been extensively used in embryotoxicity using fish embryos as promising models especially after exposure to chemical-like environmental estrogens. Bisphenol-A (BPA) is an estrogenic endocrine disruptor and is ubiquitous in the aquatic environment. Larvae of Labeo rohita were exposed to low concentrations of BPA(10, 100, 1000 μg/l) for 21 days. Innate immune system, antioxidants parameters, and developmental alterations were used as biomarkers. Exposure to BPA caused developmental abnormalities including un-inflated swim bladder, delayed yolk sac absorption, spinal curvature, and edema of pericardium. Lipid peroxidation increased and activity of catalase (p 0.05), superoxide dismutase (p 0.05), and glutathione peroxidase (p 0.01) decreased after exposure to BPA. Level of reduced glutathione also decreased (p 0.05) in BPA-exposed group. Lower expression of tumor necrosis factor-α (p 0.05) and interferon-γ (p 0.001) was observed in BPA-exposed groups while expression of interleukin-10 increased (p 0.05) in larvae exposed to 10 μg/l BPA. Moreover, exposure of BPA caused a concentration-dependent increase in expression of heat shock protein 70 (p 0.05). The present study showed that the exposure to BPA in early life stages of Labeo rohita caused oxidative stress and suppress NF-κB signaling pathway leading to immunosuppression. The results presented here demonstrate the cross talk between heat shock protein 70 and cytokines expression.