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In this study, we examined the adverse consequences of prolonged treatment with sildenafil and/or clomipramine (CLO) on the hepatic, cardiac and testicular tissues of rats. Additionally, we investigated the potential effects of treatment discontinuation. To this end, 60 adult male rats were randomly assigned into six groups and were orally treated with 4.5 mg sildenafil /kg BW (SLD) and 9 mg/ kg BW (SHD), 2.25 mg CLO/kg BW (CLO), 4.5 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SLD‐CLO) and 9 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SHD‐CLO) while the control rats received 0.5 ml distilled water for 8 weeks. Then, five rats from each group were sacrificed and the other five rats were left untreated for another four weeks to recover from the drug treatment. Long‐term administration of sildenafil and/or CLO led to oxidative stress, inflammation and structural changes in the liver, heart and testis, reduction in sperm count and motility, an increase in abnormalities, and a reduction in serum testosterone, FSH and LH levels. All tested parameters returned to the normal state following the four‐week discontinuation of sildenafil. Additionally, all the alterations caused by long‐term administration of CLO, SLD‐CLO and SHD‐CLO were significantly improved during the recovery period.

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Pharmacokinetics Doxycycline dose HPLC African catfish (Clarias gariepinus) aquaculture has experienced widespread production and has lately gained considerable interest in Egypt. Doxycycline (DOX) is used to control certain common fish's bacterial diseases, such as Septicemia, Fin rot, Columnaris, and Tail Rot. Therefore, our experiment was conducted to assess the pharmacokinetic properties of single doxycycline dose (20 mg/kg BW) orally administered in the African catfish. DOX plasma levels were measured using HPLC with a limit of detection nearly 0.035 µg/ ml, and then were undergoing compartmental analysis; a onecompartment model was detected. The doubled-peak phenomenon was identified after oral administration and the 1 st peak concentration (C max1) and the 2 nd peak concentration (C max2) in plasma were 2.29±0.46 and 1.68±0.33µg/mL at 1 st and 8 th h respectively, the absorption half-life (t 1/2ka) was 0.045 h, the elimination half-life (t 1/2ke) was 5.81 h, systemic total body clearance (Cl) was 0.72 mL/h/kg, volume of distribution of the central compartment (V d /F) was 5.74±1.11 L. These findings suggested that DOX was to some extent rapidly absorbed, widely distributed, and slowly excreted; moreover, it could be subjected to enterohepatic recycling.

Bacterial pathogens are the most serious agents causing diseases in both wild and cultured fish resulted in massive mortalities and economic losses. Motile Aeromonas Septicemia (MAS) is a prevalent bacterial disease caused by Aeromonas hydrophila (A. hydrophila) that impacts freshwater fish. This research aimed to evaluate doxycycline (DOX) antibacterial activity against A. hydrophila both in vitro and in vivo. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of DOX against A. hydrophila previously isolated from African catfish (Clarias gariepinus) were determined to be 0.78µg/mL and 3.9μg/mL, respectively. For in vivo experiment, a total number of 80 apparently healthy African catfish, were distributed randomly into four equal groups. Group 1 (non-infected, non-treated) was kept as control, Group 2 (non-infected and treated) was non-infected and treated with 20 mg/Kg BW of DOX for 5 successive days in feed, Group 3 (infected) was inoculated intraperitoneally (IP) with A. hydrophila (2× 10 8 CFU/ mL) and Group 4 (infected and treated) was infected with A. hydrophila then treated with 20 mg DOX/Kg BW. Our results revealed 70% mortality in African catfish experimentally challenged with A. hydrophila (Group 3). Moreover, significant elevation of serum alanine aminotransferase (ALT) (89±16.26, 54.67±6.44, 36±5.29 U/L, respectively), aspartate aminotransferase (AST) (195±7.64, 221.33±17.9, 211.33±12.72 U/L, respectively) and creatinine (0.68±0.098, 0.76±0.052, 0.58 ±0.023 mg/dL, respectively) was observed on 1 st , 7 th and 14 th days post treatment. While treatment of the infected fish (Group 4) with DOX decreased the mortality rate to 30 %, improved the clinical signs and significantly reduced serum ALT (30.67±6.01, 22.67±1.86 U/L, respectively) and AST (153±7.57, 147.67±6.7 U/L, respectively) on 7 th and 14 th days post treatment. Also, it significantly decreased creatinine (0.21±0.026, 0.25±0.047, 0.21±0.053 mg/dL, respectively) levels at 1 st , 7 th and 14 th days post treatment when compared with those of Group 3. The results showed that DOX could be used as an effective treatment against A. hydrophila infection in African catfish with little adverse effects.

This study investigated the possible beneficial role of the bee venom (BV, Apis mellifera L.) against zinc oxide nanoparticles (ZNPs)-induced neurobehavioral and neurotoxic impacts in rats. Fifty male Sprague Dawley rats were alienated into five groups. Three groups were intraperitoneally injected distilled water (C 28D group), ZNPs (100 mg/kg b.wt) (ZNPs group), or ZNPs (100 mg/kg.wt) and BV (1 mg/ kg.bwt) (ZNPs + BV group) for 28 days. One group was intraperitoneally injected with 1 mL of distilled water for 56 days (C 56D group). The last group was intraperitoneally injected with ZNPs for 28 days, then BV for another 28 days at the same earlier doses and duration (ZNPs/BV group). Depression, anxiety, locomotor activity, spatial learning, and memory were evaluated using the forced swimming test, elevated plus maze, open field test, and Morris water maze test, respectively. The brain contents of dopamine, serotonin, total antioxidant capacity (TAC), malondialdehyde (MDA), and Zn were estimated. The histopathological changes and immunoexpressions of neurofilament and GAP-43 protein in the brain tissues were followed. The results displayed that BV significantly decreased the ZNPs-induced depression, anxiety, memory impairment, and spatial learning disorders. Moreover, the ZNPs-induced increment in serotonin and dopamine levels and Zn content was significantly suppressed by BV. Besides, BV significantly restored the depleted TAC but minimized the augmented MDA brain content associated with ZNPs exposure. Likewise, the neurodegenerative changes induced by ZNPs were significantly abolished by BV. Also, the increased neurofilament and GAP-43 immunoexpression due to ZNPs exposure were alleviated with BV. Of note, BV achieved better results in the ZNPs + BV group than in the ZNPs/BV group. Conclusively, these results demonstrated that BV could be employed as a biologically effective therapy to mitigate the neurotoxic and neurobehavioral effects of ZNPs, particularly when used during ZNPs exposure.

Objective: The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Design: Controlled study. Animals: Seven groups of male albino rats. Procedures: Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. Group 1: injected I.P with normal saline (control), Group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), Group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, Group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and Group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. Results: The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. Conclusion and clinical relevance: The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.