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Both methotrexate and vitamin D3 are used in combination for the treatment of various diseases. The aim of this study is to highlight the effect of vitamin D3 on methotrexate-induced jejunum damage using biochemical and   histopathological  studies. Seven groups of both sexes of rats were selected and treated as follows: (Group I and Group II) : control 1,control 2 (I.P normal saline) daily for 14 and 21 days respectively ; (Group III and Group IV) :vitamin D3 groups (500 IU/rat/day) orally for 14 and 21 days, respectively;(Group V): once daily dose of methotrexate 20mg/kg, I.P injected for 4 days;(Group VI):vitamin D3 (500 IU/rat/day) once daily for 14 days and methotrexate (20 mg/kg I.P) injected only at day 10;.(Group VII) vitamin D3 (500 IU/rat/day) orally for 21 days and methotrexate (20 mg/kg I.P) injected only at day 17; then the jejunum was removed and used for measuring malondialdehyde (MDA) content, total antioxidant capacity (TAOC) level; in addition histopathological study of jejunum tissue. Administration of vitamin D3 for 21 days and a single dose of methotrexate at day 17 resulted in non-significant difference (P>0.05) in MDA; while significant reduction (P<0.05) in the TAOC level in jejunum tissue; furthermore , sever villi damage ,crypts abscess, epithelial atrophy , mixed inflammatory cells infiltrate and goblet cells depletion were observed in comparison with methotrexate group. So the study demonstrates that vitamin D3 plays a synergistic role with methotrexate therefore the combined use of vitamin D3 and methotrexate may be used as a strategy to overcome dose limitations and side effects when use for the treatment of cancer, rheumatoid arthritis and psoriasis. Key words: Jejunum damage, Methotrexate, Oxidative stress, Rats, Vitamin D3.

Lornoxicam drug is an enolic acid derivative (oxicam) of the non-steroidal anti-inflammatory drugs class. It is used to relieve pain and inflammation in rheumatic disease and osteoarthritis and other inflammation. Furthermore, such drug has side effects similar to other NSAIDs, most commonly gastrointestinal and headache. Severe but seldom adverse effects include bleeding, bronchospasms and the extremely rare Stevens-Johnson syndrome. Adverse effects on liver were not previously-investigated.Omega-3 fatty acids are poly-unsaturated fatty-acids (including α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) have roles in human physiology. They possess anti-inflammatory effect, reduce blood pressure; in addition to other health effects.The aim of this study is to investigate whether lornoxicam, omega 3 fatty acid, or co-administration of omega 3 with lornoxicam have adverse effects on liver of healthy male rats. Twenty-eight adults male rats weighing 180-200g were used in this study and the animals were randomly divided into four groups of seven rats each. Group I: negative control/rats intraperitoneally injected with normal saline in a dose 5ml/kg/day; Group II: rats intraperitoneally injected with lornoxicam at dose 0.7 mg/kg/day; Group III: rats orally-administered omega-3 only at a dose 185mg/kg/day; Group IV: rats co-administered omega-3 (185mg/kg/day) orally and intra-peritoneal injection of lornoxicam (0.7 mg/kg/day). Duration of treatment was 14-day; and at day 15 of the study, the liver of each rat was excised for the preparation of tissue-homogenate to be utilized for the estimation of ALT, AST, TNF-alpha and IL-10. Omega-3 can reduce signs of inflammation through the reduction-of TNF-alpha level and elevation of IL-10 with a significant reduction in ALT enzyme activity level in rats' liver tissue homogenate. In conclusion, Omega-3 poly-unsaturated fatty-acids may have a protective effect against hepatocytes inflammation when co-administered with lornoxicam.

Abstract:        The aim of the current study was to investigate the possible protective effect of graded doses (5, 10, and 15mg/kg) of pyridoxine hydrochloride intraperitoneally injected against (15mg/kg) doxorubicin-induced cardiotoxicity in female rats. Fifty-six (56) Wistar albino female rats were utilized weighing 180-200 gm allocated into eight groups, seven rats each; Group I: negative control distilled water; Group II: Pyridoxine (5mg/kg); Group III: Pyridoxine (10mg/kg); Group IV: Pyridoxine (15mg/kg); Group V: doxorubicin (15 mg/kg); Group VI: Pyridoxine (5 mg/kg) prior to doxorubicin (15 mg/kg); Group VII: Pyridoxine (10 mg/kg) prior to doxorubicin (15 mg/kg); Group VIII: Pyridoxine (15 mg/kg) prior to doxorubicin (15 mg/kg). DOX caused significant elevations in serum biomarker enzymes of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and significant reduction in heart tissue homogenate content of total antioxidants capacity (TAOC). Treatment with 15mg/kg pyridoxine for four consecutive days prior to a single dose 15mg/kg doxorubicin resulted in significant reduction in serum enzymes level of AST and LDH. Treatment with 10 or 15mg/kg pyridoxine for four consecutive days prior to a single dose of doxorubicin produced significant increments in TAOC heart tissue homogenate level compared to positive control. In conclusion, pyridoxine supplementation might be a promising adjunctive agent for improving oxidative stress and biological markers for preventing DOX-induced cardiac complications.

Abstract    Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy. Objective: The current study is designed to investigate effects of two different doses of zinc sulfate on mitoxantrone-induced cardiotoxicity in rats. Methods: Forty-eight (48) adult rats of both sexes were utilized in this study; the animals were randomly divided into six groups of 8 animals each. Group I: distilled water (negative control). Group II: orally-administered zinc sulfate (15mg/kg/day) Group III: orally-administered zinc sulfate (30mg/kg/day) Group IV: Intraperitoneally injected with a mitoxantrone at a dose (2.5 mg/kg) to reach total cumulative dose of 7.5 mg/kg on day 20. Group V: Orally-administered zinc sulfate at a dose (15mg/kg/day) and an intraperitoneal injection of mitoxantrone at a dose (2.5 mg/kg) was administered to reach total cumulative dose of 7.5 mg/kg on day 20. Group VI: Orally-administered zinc sulfate at a dose (30 mg/kg/day), and an intraperitoneal injection of mitoxantrone at a dose (2.5 mg/kg) to reach total cumulative dose of 7.5 mg/kg on day 20. Forty-eight (48) hr after the end of treatment duration (i.e. at day 22 nd), each animal was euthanized by diethyl ether and ketamine. Then, after cervical dislocation, blood was obtained by intracardiac puncture and then serum was prepared to estimate cardiac troponin I 3 enzyme activity levels; and the heart of each animal was excised for homogenate preparation to estimate of malondialdehyde contents. Results: Oral administration of zinc sulfate [(15mg/kg/day with total cumulative dose (7.5 mg/kg) of mitoxantrone] (Group V) resulted in a non-significant (P>0.05) difference in serum activity level of troponin I 3 enzyme and malondialdehyde contents in cardiac tissue homogenate compared to the corresponding serum enzyme activity level and contents in group of rats intraperitoneally injected with total cumulative dose of 7.5 mg/kg of mitoxantrone (Group IV). In contrast, there were significant reduction (P<0.05) in serum activity level of troponin I 3 enzyme and malondialdehyde contents in cardiac tissue homogenate of rats orally-administered zinc sulfate [(30 mg/kg/day) with total cumulative dose (7.5mg/kg) of mitoxantrone] (Group VI) compared to the corresponding enzyme activity levels and contents in group of rats intraperitoneally-injected with total cumulative dose of 7.5mg/kg of mitoxantrone (Group IV). Conclusion: zinc sulfate at a dose (30 mg/kg/day) diminishes the cardiotoxicity induced by mitoxantrone via a free radical scavenger property but it is non signifant compared to (15 mg/kg/day) .

Objective: This work was designed to investigate the effect of Vitamin E and the coenzyme Q10 (CoQ10) supplementation on neurotoxicity induced by doxorubicin (DOX) in rats.Methods: Forty-nine adult Albino rats of both sexes were utilized in this study; animals were randomly enrolled into seven groups of seven animals each. Group I: Control (rats administered corn oil); Group II: Vitamin E at a dose of 100 mg/kg/day for 3 weeks; Group III: CoQ10 at a dose of 50 mg/kg/day for 3 weeks; Group IV: DOX (2.5 mg/kg) intraperitoneally (IP) injected every other day for 2 weeks; Group V: Vitamin E (100 mg/kg/day) orally administered for 3 weeks prior to a DOX 2.5 mg/kg IP injected every other day for 2 weeks; Group VI: CoQ10 (50 mg/kg/day) for 3 weeks orally administered prior to an IP dose of DOX 2.5 mg/kg every other day for 2 weeks; and Group VII: CoQ10 (50 mg/kg/day), Vitamin E (100 mg/kg) for 3 weeks orally administered prior to an IP dose of DOX 2.5 mg/kg every other day for 2 weeks. Twenty-four hour after the end of the treatment duration, brain of each animal was excised and part of it to be utilized to prepare homogenate for the estimation of caspase-3 (CASP-3), and the remaining part is used for immunohistochemistry examination and to estimate the percent of apoptotic index by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay.Results: Vitamin E and CoQ10 significantly (p<0.05) reduced CASP-3, reduced the percent apoptotic index of TUNEL-assay, and there was an improvement in the immunohistochemistry of rats’ brain in Groups V, Group VI, and group VII by reducing number of apoptotic cells compared to Group IV.Conclusion: Both Vitamin E and CoQ10 may have a protective effect against DOX-induced neurotoxicity in rats.

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