Synthesis, COX-2 inhibition, anti-inflammatory activity, molecular docking, and histopathological studies of new pyridazine derivatives.

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1ß. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

New benzothienopyran and benzothienopyranopyrimidine derivatives as topoisomerase I inhibitors: Design, synthesis, anticancer screening, apoptosis induction and molecular modeling studies.

New benzothienopyran and benzothienopyranopyrimidine derivatives were synthesized based on the structural requirements of topoisomerase I inhibitors. All target compounds exhibited strong cytotoxic activity with GI50 range of 70.62 %-87.29 % in one dose NCI (USA) screening against 60 human tumor cell lines. Among the tested derivatives, eight compounds namely 4d, 4e, 4f, 5b, 5e, 6b, 6d, and 6f demonstrated broad spectrum and potent anticancer efficacy in five dose screening against all tested panels. DNA relaxation assay for the latter compounds showed that 4d, 5b, and 6f exhibited excellent inhibitory activity with IC50 range of 2.553-4.495 µM as compared to indenoisoquinoline reference drug (IC50 = 3.911 ± 0.21 µM). Moreover, the most active compounds were investigated for being topoisomerase poisons or catalytic inhibitors using DNA nicking assay. Compounds 4d and 6f were found to be potential Topo I poisons, whereas compound 5b has acted as Topo I suppressor. Analyzing cell cycle and induction of apoptosis for the most active compound 4d, revealed growth arrest at the S phase in MDA-MB-435 cells similarly to indenoisoquinoline reference drug. Additionally, in silico molecular modeling study for eight most active cytotoxic compounds in five dose screening demonstrated interaction with DNA as well as distinctive binding pattern similar to the reference indenoisoquinoline, indicating that the newly discovered targets are supposed to be promising candidates as Topo I inhibitors.

Synthesis of novel nicotinic acid derivatives of potential antioxidant and anticancer activity.

This study comprises the design and synthesis of novel nicotinic acid-based cytotoxic agents with selective inhibitory efficacy against the vascular endothelial growth factor receptor-2 (VEGFR-2). Screening of novel compounds for cytotoxicity was assessed against 60 human cancer cell lines. The two most active compounds, 5b and 5c, and the reference drugs sorafenib and doxorubicin were investigated against HCT-15, PC-3, and CF-295 cancer cell lines. Compound 5c exhibited the highest cytotoxic potential compared to doxorubicin against the HCT-15 and PC-3 tumor cell lines. Moreover, it exhibited higher cytotoxic potential and selectivity toward the HCT-15 cell panel compared with sorafenib. Compound 5c demonstrated promising VEGFR-2 inhibition (concentration needed to inhibit cell viability by 50%, IC50 = 0.068 µM) and superior VEGFR-2 selectivity over the epidermal growth factor receptor and platelet-derived growth factor receptor-ß enzymes. It also reduced the total and phosphorylated VEGFR-2 and induced apoptosis, as evidenced by a 4.3-fold rise in caspase-3 levels. The antioxidant potential of the new compounds was determined via measuring the superoxide dismutase (SOD) levels, among which compound 5c exhibited an SOD level almost comparable to ascorbic acid. These results suggested that compound 5c exhibited dual cytotoxic and antioxidant activities. Docking of 5c into the VEGFR-2 pocket showed a similar binding mode to sorafenib. Moreover, the ADME (absorption, distribution, metabolism, and excretion) profile of 5c outlined drug-likeness. Finally, The density functional theory calculations displayed an increased binding affinity of 5c to the target enzyme.

Pyridazine derivatives as selective COX-2 inhibitors: A review on recent updates.

Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development of powerful COX-2 inhibitors, particularly when selectively functionalized. This article summarizes some methods for the synthesis of pyridazine derivatives. Furthermore, it covers all of the pyridazine derivatives that have appeared as selective COX-2 inhibitors, making it useful as a reference for the rational design of novel selective COX-2 inhibitors.

Platelet-rich fibrin a new approach in management of persistent oral ulcers in blistering skin diseases.

The present study designed to evaluate the healing power of platelet-rich fibrin (PRF) in terms of pain control and mucosal repair. A randomised, controlled, pilot clinical trial was conducted on 16 patients randomly distributed with 1:1 allocation ratio into two groups. The treatment group received PRF minced and mixed with orabase and the control group received clobetasol propionate 0.05% mixed with orabase. Pain reduction was evaluated as primary outcome along with mucositis healing as secondary outcome. A statistically significant difference in pain reduction was observed between the two groups (p ≤ 0.05). The clinical results at Day 7 has shown that PRF group had 100% pain reduction while, CP group had 32.5% reduction from base line. PRF offered superior clinical results providing rapid pain alleviation and accelerated ulcer healing compared to corticosteroids.

Anti-inflammatory activity of pyridazinones: A review.

The pyridazinone core has emerged as a leading structure for fighting inflammation, with low ulcerogenic effects. Moreover, easy functionalization of various ring positions of the pyridazinone core structure makes it an attractive synthetic and therapeutic target for the design and synthesis of anti-inflammatory agents. The present review surveys the recent advances of pyridazinone derivatives as potential anti-inflammatory agents to provide insights into the rational design of more effective anti-inflammatory pyridazinones.

Synthesis, molecular modeling and biological evaluation of new benzo[4,5]thieno[3,2-b]pyran derivatives as topoisomerase I-DNA binary complex poisons.

A series of new benzo[b]thiophenes 2a-f and benzo[4,5]thieno[3,2-b]pyran derivatives 3a-f and 4a-f were synthesized and their structures were confirmed by elemental analyses and spectral data. All synthesized compounds were evaluated by the National Cancer Institute (NCI, USA) against 60 human tumor cell lines. Compounds 3a-f and 4a-f showed potent cytotoxic effects in one dose assay with mean growth inhibition ranging from 62% to 80%. Six compounds 3a, 3d, 3e, 3f, 4d and 4e were selected by NCI, USA for five dose evaluation against 60 human tumor cell lines. Compounds 3a, 3d, 3e and 3f exhibited very potent and broad spectrum cytotoxicity against almost all cancer cell lines with mean concentration that yield 50% growth inhibition (MG-MID GI50) of 0.1-0.58 µM and mean concentration that produce 100% growth inhibition (MG-MID TGI) of 6.03-10.00 µM. Compounds 4d and 4e exhibited very potent and selective cytotoxic activity against MDA-MB-435 subpanel (melanoma cancer) with GI50 of 0.45 µM and 0.59 µM, respectively. The mechanism of antiproliferative activity was determined for the most active compounds 3a, 3d, 3e, 3f, 4d, and 4evia measuring their half maximal inhibitory concentration (IC50) against topoisomerase I enzyme at different concentrations. Compounds 3a and 3e exhibited excellent activity compared with reference drugs with IC50 of 0.295 µM and 0.219 µM, respectively. Plasmid DNA nicking assay verified that these compounds are topoisomerase I poisons not suppressors. The active compound 3e induced a significant disruption in the cell cycle profile parallel to its effect on apoptosis induction.

Synthesis and biological evaluation of new nicotinate derivatives as potential anti-inflammatory agents targeting COX-2 enzyme.

Two novel series derived from nicotinic acid were synthesized and evaluated for their inhibitory activity against cyclooxygenases COX-1 and COX-2, and their selectivity indices were determined. Celecoxib, diclofenac and indomethacin were used as reference drugs. All compounds showed highly potent COX-2 inhibitory activity and higher selectivity towards COX-2 inhibition compared to indomethacin. In addition, these compounds except 3a showed clear preferential COX-2 over COX-1 inhibition compared to diclofenac. Compounds 3b, 3e, 4c and 4f showed COX-2 inhibitory activity equipotent to celecoxib. Compounds 4c and 4f demonstrated selectivity indices 1.8-1.9 fold higher than celecoxib. These two most potent and COX-2 selective compounds were further tested in vivo for anti-inflammatory activity by means of carrageenan induced rat paw edema method. Ulcerogenic activity with histopathological studies were performed. The results showed no ulceration, which implies their safe gastric profile. Compound 4f exhibited the most potent in vivo anti-inflammatory activity comparable to all reference drugs. Further, compounds 4c and 4f were investigated for their influence on certain inflammatory cytokines TNF-α and IL-1ß in addition to PEG2. The findings revealed that these candidates could be identified as promising potent anti-inflammatory agents. Molecular docking of 4c and 4f in the COX-2 active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of celecoxib, explaining their remarkable COX-2 inhibitory activity.

New benzothieno[2,3-c]pyridines as non-steroidal CYP17 inhibitors: design, synthesis, anticancer screening, apoptosis induction, and in silico ADME profile studies.

A series of [1]benzothieno[2,3-c]pyridines was synthesised. Most compounds were chosen by NCI-USA to evaluate their anticancer activity. Compounds 5a-c showed prominent growth inhibition against most cell lines. 5c was selected at five dose concentration levels. It exhibited potent broad-spectrum anticancer activity with a GI50 of 4 nM-37 µM. Cytotoxicity of 5a-c was further evaluated against prostate, renal, and breast cancer cell lines. 5c showed double and quadruple the activity of staurosporine and abiraterone, respectively, against the PC-3 cell line with IC50 2.08 µM. The possible mechanism of anti-prostate cancer was explored via measuring the CYP17 enzyme activity in mice prostate cancer models compared to abiraterone. The results revealed that 5c suppressed the CYP17 enzyme to 15.80 nM. Moreover, it was found to be equipotent to abiraterone in testosterone production. Cell cycle analysis and apoptosis were performed. Additionally, the ADME profile of compound 5c demonstrated both good oral bioavailability and metabolic stability.

New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation.

New pyridazinone and pyridazinthione derivatives were designed, synthesized and identified through performing 1H NMR, 13C NMR, IR and MS spectroscopic techniques. All the newly synthesized derivatives were evaluated for cyclooxygenase inhibitory activity and COX-2 selectivity using celecoxib and indomethacin, as reference drugs. All compounds showed highly potent COX-2 inhibitory activity with IC50 values in nano-molar range. Moreover, they demonstrated higher selectivity towards COX-2 inhibition compared to indomethacin. Compounds 3d, 3g and 6a exhibited significantly increased potency towards COX-2 enzyme compared to celecoxib with IC50 values of 67.23, 43.84 and 53.01 nM, respectively. They were 1.1-1.7 folds more potent than celecoxib (IC50 = 73.53 nM) and extremely much more potent than indomethacin (IC50 = 739.2 nM). Of particular interest, Compound 3g showed SI of 11.51 which was as high as that of celecoxib (SI 11.78). This compound was further challenged by in vivo anti-inflammatory activity assay and gastric ulcerogenic effect. It showed comparable anti-inflammatory activity to indomethacin as positive control. Moreover, the anti-inflammatory activity of compound 3g was found to be equipotent to celecoxib. Furthermore, the selective COX-2 inhibitor 3g exhibited a superior gastrointestinal safety profile compared to the reference drugs celecoxib and indomethacin with less number of ulcers and milder ulcer score. The molecular docking study of this compound with COX-2 protein revealed more favorable binding mode compared to celecoxib, explaining its remarkable COX-2 inhibitory potency.

Triazolopyridazine derivatives: Synthesis, cytotoxic evaluation, c-Met kinase activity and molecular docking.

Novel series of some triazolo[4,3-b]pyridazine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated for their cytotoxic activity at 10-5 M concentration towards 60 cancer cell lines according to USA NCI protocol. Most of the synthesized compounds showed good activity against SR (leukemia) cell panel. The most active compounds, 2f and 4a were subjected for further evaluation at a five dose level screening and their efficacy for c-Met kinase inhibition was determined in vitro. Binding mode of these derivatives was explored via molecular docking.

New 3-Substituted-2-(4-hydroxyanilino)pyridine Derivatives: Synthesis, Antitumor Activity, and Tubulin Polymerization Inhibition.

A series of new pyridine derivatives 4a-c, 5a-d, 6a-d, 7a-f, and 8a-f structurally related to ABT-751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT-116 and HepG-2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC50 = 0.52 and 1.40 µM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine.

NSAIDs between past and present; a long journey towards an ideal COX-2 inhibitor lead.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity.

Design, synthesis, biological evaluation, and docking studies of novel triazolo[4,3-b]pyridazine derivatives as dual c-Met/Pim-1 potential inhibitors with antitumor activity.

Interest has been piqued in c-Met and Pim-1, potential new cancer treatment targets. A variety of triazolo[4,3-b]pyridazine derivatives were synthesized to create powerful dual c-Met/Pim-1 inhibitors having the pharmacophoric elements of both enzyme inhibitors. All derivatives were screened for their cytotoxic effects on 60 cancer cell lines. Compounds 4g and 4a, had strong antiproliferative cytotoxic impacts on tumor cells, with mean GI% values of 55.84 and 29.08%, respectively. Research revealed that 4g has more powerful inhibitory activity against c-Met and Pim-1, with IC50 of 0.163 ± 0.01 and 0.283 ± 0.01 µM, respectively than the reference and derivative 4a. Moreover, compound 4g was the subject of an additional investigation into biological processes. The findings showed that compound 4g caused MCF-7 cells to arrest in the S stage of the cell cycle. Also, it accelerated the progress of apoptosis 29.61-fold more than the control. Compound 4g demonstrated a significantly higher level of caspase-9 and a decreased level of p-PI3K, p-AKT, and p-mTOR compared to staurosporine. Later, analysis of 4g showed good drug-ability and pharmacokinetic properties. A similar mode of interaction at the ATP-binding site of c-Met and Pim-1 compared to the docked ligands was suggested by additional docking studies of compound 4g.

Hexavalent chromium ion removal from wastewater using novel nanocomposite based on the impregnation of zero-valent iron nanoparticles into polyurethane foam.

In this study, we developed a novel nanocomposite, polyurethane foam impregnated with zero-valent iron nanoparticles (PU@nZVI), for the effective removal of chromium(VI) from various water sources. The characterization of nanocomposite (PU@nZVI) was performed by XRD, SEM-EDS, TEM and FT-IR techniques. Using the response surface methodology, we optimized the removal conditions, achieving an optimal pH of 2 and a dose of 0.5 g/L. The PU@nZVI demonstrated an excellent maximum adsorption capacity of 600.0 mg/g for Cr6+. The adsorption kinetics and isotherms were best described by the pseudo-second-order model and the Freundlich isotherm, respectively. Significantly, the nanocomposite removed 99.98% of Cr6+ from tap water, 96.81% from industrial effluent, and 94.57% from treated sewage wastewater. Furthermore, the PU@nZVI maintained its efficiency over five adsorption-desorption cycles, highlighting its reusability. These results suggest that the PU@nZVI nanocomposite is a highly efficient and sustainable option for chromium(VI) removal in water treatment applications.

The impacts of dietary inclusion of soybean oil and linseed oil on growth performance, carcass yield, and health status of growing Japanese quail.

Polyunsaturated fatty acids (PUFA), including n-6 and n-3 fatty acids, are essential for enhancing the performance and health of poultry. Avian species lack desaturase enzymes for endogenous synthesis of n-6 and n-3 fatty acids. This work aimed to determine the impacts of including soybean oil (SO) and linseed oil (LO) in quail diets on growth, lipid profile, hepatic and renal functions, immunity, and antioxidant status. A total of 350 Japanese quail chicks (1-wk-old) were randomly arranged into 7 dietary treatment groups. Seven isocaloric and isonitrogenous experimental basal diets were formed based on the nutritional requirements of growing Japanese quail. Group 1, the control, received a basal with no oils, while groups 2 to 7 received a basal diet containing either 1% SO, 1.5% SO, 2% SO, 1% LO, 1.5% LO, or 2% LO, respectively. Quail groups that consumed diets containing LO at all levels showed significantly greater live body weight (LBW) at 5th wk of age than other experimental groups. The dietary incorporation of 1.5 or 2% SO or LO at all levels yielded significant improvements in body weight gain (BWG) and feed conversion ratio (FCR) through 3 to 5 and 1 to 5 wk of age. Different dietary oil sources and levels have no significant impacts on feed intake (FI) and carcass yield parameters. Lipid profile parameters were improved by adding SO and LO in quail diets, with LO having a higher effect than SO. The hepatic and renal functionality were improved by adding SO and LO in quail diets. The lowest uric acid (UA) bloodstream concentrations were recorded in the quail group fed a diet with 2% LO. Values of Gamma globulins (G-GLO) and immunoglobulins (G, M, and A) were increased by adding SO or LO to quail diets. Blood levels of MDA and TAC were improved significantly by including LO in quail diets. The activity of the superoxide dismutase (SOD) enzyme was significantly increased by adding SO or LO to quail diets. Generally, adding SO or LO to growing quail diets up to 2% could yield favorable effects on growth performance, blood lipids, hepatic and renal functions, immunity, and antioxidant status; however, LO seems to have better effects than SO.

Efficacy and safety of etrolizumab in treatment of moderate to severe ulcerative colitis: A systematic review and meta-analysis.

Background: Etrolizumab is a promising drug for treating moderate to severe ulcerative colitis. Aim: The aim of this study was to assess the efficacy and safety of etrolizumab for induction and maintenance of remission in moderate to severe ulcerative colitis. Methods: We searched the following databases: PUBMED, Web of Science, OVID, and SCOPUS from inception to January 15. Inclusion criteria were any phase 2 and 3 clinical trials that compared etrolizumab with a placebo in treating moderate to severe ulcerative colitis, excluding case reports, animal studies, phase 1 trials, and conference abstracts due to duplication. We used RevMan software (5.4) for the meta-analysis. Results: Five clinical trials were included in our meta-analysis. The total number of patients included in the study is 1248 patients, 860 patients in the etrolizumab group and 388 patients in the placebo group. In the induction phase, the pooled analyses showed a statistically significant association between etrolizumab and increased clinical remission, and endoscopic remission compared with placebo (risk ratio [RR] = 2.66, 95% confidence interval [CI] = 1.69-4.19, p < 0.0001), and (RR = 2.35, 95% CI = 1.52-3.65, p = 0.0001), respectively. In the maintenance phase, the pooled analyses showed a statistically significant association between etrolizumab and increased histologic remission and endoscopic remission (RR = 2.04, 95% CI = 1.40-2.98, p = 0.0002) and (RR = 1.92, 95% CI = 1.29-2.85, p = 0.001), respectively. No statistically significant difference was observed in adverse events between etrolizumab and placebo in the induction and maintenance phases. Conclusion: Our results show that etrolizumab is an effective and safe drug for the induction and maintenance of clinical remission in moderate to severe ulcerative colitis patients, as proved by histologic and endoscopic findings. Future randomized trials are still needed to compare etrolizumab to the other agents and further establish its value for the practice.

Mental distress links with physical activities, sedentary lifestyle, social support, and sleep problems: A Syrian population cross-sectional study.

Background: Mental diseases are very widespread and difficult to treat, affecting around 12% of the global population in 2019. Since social interaction is crucial to human existence and loneliness has been proven to be a significant predictor of depressive symptoms, it stands to reason that social connection problems would also contribute to depression. Physical inactivity seems to weaken and aggravate insulin tolerance alterations, glucose homeostasis, and plasma triglyceride levels, thereby influencing one's mood and happiness. This suggests that physical inactivity may be a significant risk factor for mental illness. This research contributes to our understanding of the mental health situation in Syria by exploring associations between a set of measurable characteristics that may be adjusted. Methods: An online quantitative cross-sectional study was conducted between March and April 2022 in Syria, using a structured questionnaire that assesses data on behaviors of health, health in general, wellbeing, and adult population quality of life. Results: Among 1,224 respondents (371 men and 853 women), women have shown higher levels of mental distress, sleep issues, low engagement in structured activities, and a difficult work environment than men. Women experiencing mental anguish have reported being more sedentary, participating in less scheduled activities, and receiving less social support. Conclusions: There are observable connections between high sedentary time and women experiencing mental distress. The mental health of Syrian women in distress was associated with a lack of participation in both organized activities and physical exercise in their free time. Furthermore, sleep issues and financial troubles were seen in persons with mental diseases of both males and females.

Mitigating the Growth, Biochemical Changes, Genotoxic and Pathological Effects of Copper Toxicity in Broiler Chickens by Supplementing Vitamins C and E.

This experiment was carried out to explore the efficiency of an individual or combined doses of vitamin C (Vit. C) and vitamin E (Vit. E) in alleviating biochemical, genotoxicity, and pathological changes in the liver induced by copper sulfate (CuSO4) toxicity in broiler chickens. Two hundred and fifty-one-day-old broiler chicks were haphazardly allotted into five groups (five replicates/group, ten chicks/replicate). The birds were fed five experimental diets; (1) basal diet with no additives (CON), (2) basal diets supplemented with 300 mg CuSO4/kg diet (CuSO4), (3) basal diets supplemented with 300 mg CuSO4/kg diet + 250 mg Vit. C /kg diet, (4) basal diets supplemented with 300 mg CuSO4/kg diet +250 mg Vit. E /kg diet, (5) basal diets supplemented with 300 mg CuSO4/kg diet + 250 mg Vit. C /kg diet + 250 mg Vit. E /kg diet for six weeks. The results displayed that CuSO4-intoxicated birds had significantly (p < 0.05) decreased bodyweight, weight gain, and feed intake with increased feed conversion ratio from the 2nd week till the 6th week compared with the CON. However, these changes were minimized by single or combined supplementation of vitamin C and E. The FCR was insignificantly different in birds-fed diets complemented with vitamin C and E singly or in combination from the 3rd week of age compared to the CON. Serum aminotransferases (ALT, AST) and alkaline phosphatase (ALP) were elevated in CuSO4-intoxicated birds (p < 0.05). Additionally, they showed a drop in serum total protein (TP), albumin, globulins, triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels compared to the CON (p < 0.05). Concomitantly, histopathological and DNA changes were perceived in the liver of CuSO4-intoxicated birds. Co-supplementation of Vit. C and Vit. E single-handedly or combined with CuSO4-intoxicated chickens enhanced the performance traits and abovementioned changes, especially with those given combinations of vitamins. From the extant inquiry, it could be established that supplementation of vitamin C and E was beneficial for mitigating the harmful effects of CuSO4 toxicity on growth performance and liver histoarchitecture in broiler chickens.