Abstract
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.
Highlights
Methotrexate (MTX), a folic acid antagonist, inhibits the enzyme dihydrofolate reductase (DHFR) and it is utilized as an antineoplastic and anti-rheumatoid agent [1]
For histopathological study in the jejunum tissue of control 1 (Group I), and control 2 (Group II) of rats, there were normal appearance of villi and crypts, with no epithelial atrophy,but a mild– moderate degree of mixed inflammatory cells infiltrate were seen within lamina propria; no goblet cell depletion was observed in Figure 3 (A and B)
In group of rats orally-administered vitamin D3 for 14 days (Group III), there wasa mild-villous and crypts damage, -epithelial atrophy, and –mixed inflammatory cells infiltrate were seen in the lamina propria; mild goblet cells depletion was observed (Figure 3-C)
Summary
Methotrexate (MTX), a folic acid antagonist, inhibits the enzyme dihydrofolate reductase (DHFR) and it is utilized as an antineoplastic and anti-rheumatoid agent [1]. It has been reported that different in vitro and in vivo studies have shown that OS and dysregulation of antioxidant enzymes can play an important role in MTX-induced jejunal damage [3, 4]. The primary sites of action of such vitamin are the intestine, bone, and kidneys; the biologic functions of vitamin D3 are multiple and include its classic role in bone and mineral metabolism, and other non-classic actions, including cell proliferation, immunomodulation and cell differentiation [8].Vitamin D3 implicated in the pathophysiology of immune-mediated diseases including multiple sclerosis (MS) and inflammatory bowel disease (IBD) and it insufficiency has been linked to higher rates of cancers including colorectal, prostate and breast cancers [9,10]. Objective: This study aims to study the effect of vitamin D3 at two different administration durations against MTX-induced jejunal damage in rats using biochemical and histopathological studies
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