Epidemiological studies have shown an association between disinfection by‐products (DBP) of drink... more Epidemiological studies have shown an association between disinfection by‐products (DBP) of drinking water chlorination (DWC) and adverse pregnancy outcomes (APO) and indicated the involvement of DBP‐induced developmental toxicity on fetal brains. However, the precise mechanisms involved are not known. We report that dichloroacetonitrile (DCAN), a DBP of DWC, induces protein carbonylation in immortalized rat cortical astrocyte cells CTX‐TNA2 and pathological changes in the brains of fetuses of DCAN‐exposed pregnant albino mice. Exposure of cells to DCAN for 48 hr resulted in increased superoxide generation, decreased GSH/GSSG ratio, protein carbonylation, and inhibition of proteasomal activity. Oral administration of DCAN to pregnant mice resulted in low fetal body weight, neurodegeneration in the fetal cerebral cortex, redox imbalance and induction of apoptosis in the cerebral cortex and the cerebellum of the fetuses. Our data suggest that DCAN induces oxidative protein modificatio...
Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. D... more Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. Developing new therapies to manage BPH with improved efficacy and safety is strongly needed. In this regard, auraptene is a natural compound with multiple pharmacological effects, but with poor oral bioavailability. This investigation aimed to assess the possible protection offered by auraptene-nanostructured lipid carrier (auraptene-NLC) in a BPH model induced by testosterone in rats. Auraptene-NLC had optimum particle size and drug release profile compared to raw auraptene. At doses (5 and 10 mg/kg), it hampered the rise in prostatic weights & indices relative to rats challenged with testosterone. Moreover, auraptene-NLC alleviated histopathological abnormalities in prostate architecture and decreased the glandular epithelial height. Additionally, testosterone-induced oxidative stress was alleviated by auraptene-NLC and inhibited raised lipid peroxidation, catalase and superoxide dismutase exhaustion as well as enhanced glutathione content. Moreover, it significantly reduced the prostate content of nuclear factor κB, Interleukins1β & 6, as well as transforming growth factor β, compared to testosterone group. The proapoptotic activity of auraptene-NLC (10 mg/kg) was confirmed by a significant increase of prostate cleaved caspase-3, boosted Bax/Bcl2 mRNA ratio that was further confirmed by assessing their protein expressions. Furthermore, the beneficial effects of auraptene-NLC against BPH were substantiated by ameliorating testosterone-induced decline of nuclear PPARα & PPARγ and inhibiting the increased expression of cyclin D1 protein. In conclusion, auraptene-NLC offers a protective effect in rats whereby BPH was induced by testosterone, via its anti-inflammatory, antioxidant and proapoptotic activities, and PPAR family activation.
A dysregulation of the wound healing process can lead to the development of various intractable u... more A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of IL-6, IL-1β, and TNF-α pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase HIF-1α and TGF-β1 proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-β receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-β1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.
Epidemiological studies have shown an association between disinfection by‐products (DBP) of drink... more Epidemiological studies have shown an association between disinfection by‐products (DBP) of drinking water chlorination (DWC) and adverse pregnancy outcomes (APO) and indicated the involvement of DBP‐induced developmental toxicity on fetal brains. However, the precise mechanisms involved are not known. We report that dichloroacetonitrile (DCAN), a DBP of DWC, induces protein carbonylation in immortalized rat cortical astrocyte cells CTX‐TNA2 and pathological changes in the brains of fetuses of DCAN‐exposed pregnant albino mice. Exposure of cells to DCAN for 48 hr resulted in increased superoxide generation, decreased GSH/GSSG ratio, protein carbonylation, and inhibition of proteasomal activity. Oral administration of DCAN to pregnant mice resulted in low fetal body weight, neurodegeneration in the fetal cerebral cortex, redox imbalance and induction of apoptosis in the cerebral cortex and the cerebellum of the fetuses. Our data suggest that DCAN induces oxidative protein modificatio...
Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. D... more Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. Developing new therapies to manage BPH with improved efficacy and safety is strongly needed. In this regard, auraptene is a natural compound with multiple pharmacological effects, but with poor oral bioavailability. This investigation aimed to assess the possible protection offered by auraptene-nanostructured lipid carrier (auraptene-NLC) in a BPH model induced by testosterone in rats. Auraptene-NLC had optimum particle size and drug release profile compared to raw auraptene. At doses (5 and 10 mg/kg), it hampered the rise in prostatic weights & indices relative to rats challenged with testosterone. Moreover, auraptene-NLC alleviated histopathological abnormalities in prostate architecture and decreased the glandular epithelial height. Additionally, testosterone-induced oxidative stress was alleviated by auraptene-NLC and inhibited raised lipid peroxidation, catalase and superoxide dismutase exhaustion as well as enhanced glutathione content. Moreover, it significantly reduced the prostate content of nuclear factor κB, Interleukins1β & 6, as well as transforming growth factor β, compared to testosterone group. The proapoptotic activity of auraptene-NLC (10 mg/kg) was confirmed by a significant increase of prostate cleaved caspase-3, boosted Bax/Bcl2 mRNA ratio that was further confirmed by assessing their protein expressions. Furthermore, the beneficial effects of auraptene-NLC against BPH were substantiated by ameliorating testosterone-induced decline of nuclear PPARα & PPARγ and inhibiting the increased expression of cyclin D1 protein. In conclusion, auraptene-NLC offers a protective effect in rats whereby BPH was induced by testosterone, via its anti-inflammatory, antioxidant and proapoptotic activities, and PPAR family activation.
A dysregulation of the wound healing process can lead to the development of various intractable u... more A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of IL-6, IL-1β, and TNF-α pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase HIF-1α and TGF-β1 proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-β receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-β1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.
Uploads
Papers by Ashraf Abdel-Naim