Management of Short Bowel Syndrome in Nigerian Dogs

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1 ORGINAL ARTICLE pii: S Received: 04 Apr 2018 Accepted: 08 My , Scienceline Publiction World s Veterinry Journl World Vet J, 8(2): 3447, June 25, 2018 ISSN Mngement of Short Bowel Syndrome in Nigerin Dogs Aboh Iku Kisni 1 *, John Byo Adeynju 2, Abdullhi Teleh Els 1 nd Mmmn Legbo Sonfd 3 1 Deprtment of Veterinry Surgery nd Theriogenology, College of Veterinry Medicine, University of Agriculture, Mkurdi Benue Stte, Nigeri 2 Deprtment of Veterinry Surgery nd Rdiology, Fculty of Veterinry Medicine University of Ilorin, Nigeri 3 Deprtment of Veterinry Antomy, Fculty of Veterinry Medicine, Usmnu Dnfodiyo University, Sokoto, Nigeri * Corresponding uthor s Emil: bohkisni@yhoo.com ABSTRACT The effects of glutmine, honey, scorbic cid nd glutmine, honey, scorbic cid combintion on smll bowel dpttion following 70% smll intestinl resection in locl Nigerin dogs were investigted. Thirty dult dogs with medin weight of 12.4kg (rnge 718 kg) were used in this study. The dogs were rndomized into five groups of six dogs ech following resection. Group 1 is the control group. The dogs here were not plced on ny tretment. Group 2 dogs were plced on glutmine. Group 3 dogs were plced on honey. Group 4 dogs were plced on scorbic cid nd group 5 dogs were plced on glutmine, honey nd scorbic cid combintion. Intestinl biopsy smples were collected t dy 0, 4 weeks, 6 weeks nd 8 weeks for histomorphometric study. Intestinl morphology ws evluted using light microscopy. The body weights of the dogs were monitored weekly for 4, 6 nd 8 weeks in the five groups. Smll intestinl dptive response ws evluted t 4, 6 nd 8 weeks post surgery. The nimls treted with glutmine, honey, scorbic cid nd glutmine/ honey/ scorbic cid combintion experienced increse in intestinl villus height, villus width, crypt depth nd wll thickness. The control group experienced fll in intestinl villus height, villus width, crypt depth nd wll thickness. The nimls treted with glutmine, honey, scorbic cid combintion showed better therpeutic response followed by glutmine, honey nd scorbic cid in tht order. There ws grdul increse in the body weight of nimls in these groups. The control group did not show ny pprecible dptive response nd the nimls in this group progressively lost weight. It ws concluded tht dogs presented with short bowel syndrome could benefit from the supplementtion of glutmine, honey nd scorbic cid in food. Key words: Short bowel syndrome, Totl prenterl nutrition, Intestinl resection, Smll intestinl dptive response INTRODUCTION Extensive resection of the smll intestine cn result in condition known s Short Bowel Syndrome (SBS) (Gormn et l., 2006; Hsosh et l., 2008; Seethrm nd Rodrigues, 2011; Myeur et l., 2016; Vgholkr et l., 2016) nd it occurs in both humns nd nimls. It is disorder chrcterized by n intestinl bsorptive surfce re tht is insufficient to support the host. This intestinl loss results in the mlbsorption of fluid, electrolytes nd other essentil nutrients, severe dirrhe, dehydrtion nd progressive mlnutrition. Intestinl filure results when the residul bowel length cnnot meet the ptient s nutritionl requirement thus necessitting dependence on prenterl nutrition (PN) (Donohoe nd Reynolds, 2010; Norholk et l., 2012; Winkler nd Smith, 2014; Myer nd Kerner, 2017). It is this dependence on prenterl nutrition tht is responsible for the mjority of morbidity nd mortlity ssocited with short bowel syndrome (Wles nd ChristisonLgy, 2010; Vipperl nd O keefe, 2014). In dogs, intestinl resection is done becuse of liner foreign bodies, mesenteric volvulus, direct trumtic dmge to the smll bowel wll, solitry foreign body with perfortion of the intestine, intussusceptions, dehiscence of previous gstrointestinl trct surgery site nd gstrointestinl trct tumor (Gormn et l., 2006). Long term survivl of ptients with SBS is dependent on the dpttion of the remining smll intestine nd response to phrmcologicl nd nutritionl mngement (Wll, 2013, CunhMelo nd Cost, 2014; RodriguezMontes et l., 2016). Mnging short bowel syndrome is chllenging s the medictions re expensive nd ptients hve to use them for very long time nd there is no gurntee tht the response will be fvourble (Hrbty et l., 2004). 34

2 MATERIALS AND METHODS Experimentl nimls Thirty dogs under 2 yers of ge with men weight of 12.4 kg (rnge 718 kg) were used for this study. They were stbilized for 4 weeks by being borded in kennels within the teching hospitl nd were dewormed nd treted ginst ectoprsites nd hemoprsites. They were fed dily nd wter ws provided d libitum. Ech niml ws fsted for 12 hours prior to surgery. They were premedicted with Atropine sulphte (Jingsu Huyng phrmceuticl, Chin) t dose rte of 0.04 mg/kg nd xylzine hydrochloride (XYLM2, VMD, Belgium) t dose rte of 1 mg/kg body weight intrmusculrly. Induction ws done with thiopentone sodium (Rotexmedic, Germny) t dose rte of 10 mg/kg body weight intrvenously. The totl smll intestinl length in ech dog ws clculted nd recorded s described by Kisni et l. (2017). Surgicl procedure Ech niml ws septiclly prepred nd ventrl midline bdominl incision ws mde. The intestinl trct ws exteriorized. Seventy per cent of the smll intestinl trct (from the result of the preliminry study) ws resected beginning from point 7cm from the duodunojejunl flexure (treitz ligment). The residul intestinl trct ws sutured using end to end nstomosis with polyglctin 910 (vicryl Ethicon, USA) size 0 s described erlier. A full thickness biopsy smple of the smll intestinl trct (Jejunum nd ileum) were collected nd fixed in 10% formlin (pretretment smple). The nstomostic site ws covered with omentum nd returned to the bdominl cvity. The bdominl incision ws closed using stndrd surgicl technique (Fossum, 2014). Procin penicillin (Shuzhung co ltd, Chin) 20,000 iu/kg nd Streptomycin (North Chin phrmceuticl co ltd, Chin)(10 mg/kg) ws dministered intrmusculrly for 5 dys post opertive. Pentzocin (Bhrt Prenterls ltd, Indi) ws dministered intrmusculrly t the dose rte of 5mg/kg for 7 dys to relieve pin. The dogs were given 5% dextrose infusion intrvenously t 10 mls/kg/hr on the second nd third dy post opertive. They were fed blnd diet gruel on the fourth post opertive dy nd returned to norml solid diet on dy five post surgery. After surgery, the nimls were rndomized into five groups tht ech group contined six nimls. Group 1 ws the control group. The nimls in this group were not treted. They were left to ttend to their norml dily rtion throughout the period of experiment. Group 2: Animls in this group were plced on orlly dministered glutmine. The dogs were given 9.0 mg/kg/dy for 4 weeks (two dogs), 12.0 mg/kg/dy for 6 weeks (Two dogs) nd two15.0 mg/kg/dy for 8 weeks (two dogs). Group 3: The nimls in this group were plced on orlly dministered honey. Two dogs were plced on honey t 7.5 mls/dy for 4 weeks, two dogs consumed10mls/dy for 6 weeks nd two dogs were dministered 12.5 mls/dy for 8 weeks. Group 4: The nimls in this group were plced on orlly dministered Ascorbic cid (vitmin C). Two dogs were dministered scorbic cid 150 mg/dy for 4weeks, two dogs dministered on scorbic cid 250mg/dy for 6 weeks nd two dogs dministered 350 mg/dy for 8 weeks. Group 5: The nimls in this group were plced on combine dose of glutmine (9 mg/kg/dy), honey (7.5 mls/dy) nd vitmin C (150 mg/dy). Two nimls were plced on this combintion for 4 weeks, two nimls dministered for 6weeks nd two nimls dministered for 8 weeks. Histomorphometric nlysis Smll bowel biopsy specimens were obtined from the jejunum nd ileum t dy 0 (presurgicl) nd t 4, 6 nd 8 weeks post resectionnstomosis. A totl of four biopsy specimens were obtined from ech ptient (t the end of first nd second lprotomy) nd plced in 10% formlin. After routine formlin fixtion, biopsy specimens were embedded in prffin. Fourmicrometerthick (4 µm) sections were cut perpendiculr to the mucos nd stined routinely with H&E. Then using light microscopy nd n eye piece micrometer t mgnifiction of 100, the villus height, villus width, crypt depth nd cross sectionl re of the bowel mucos were mesured s explined by Joquim et l. (2005). Five redings were tken for ech prmeter nd the verge vlue determined. Photomicrogrph nd interprettion of the slides were done using trinoculr microscope nd Amscope Toup View 3.7. Sttisticl nlysis Dt were expressed s descriptive sttistics. Differences mong the groups were evluted using one wy nlysis of vrince (ANOVA) followed by two tiled student s ttest using SPSS version 16. The level of significnce ws set t 5%. Ethicl pprovl This study ws pproved by the ethicl committee of the college of veterinry medicine, university of Agriculture, mkurdi, Nigeri with no

3 RESULTS Histomorphometry Villus height There ws n increse in villus height for ll the groups except the control group which experienced fll in jejun villus height in week 6 nd 8 (Tble 1) nd fll in ilel villus height in week 4 nd 6. Group 5 lso experienced fll in jejun villus height in week 6 (Tble 5). The nimls in group 4 showed fll in ile villus height in week 6. Groups 2, 3, nd 5 showed sttisticlly significnt increse in villus height (Tbles 2, 3 nd 5) (P<0.05) while groups 1 nd 4 did not cuse sttisticl increse in villus height (Tbles 1 nd 4) (P>0.05). Villus width There ws increse in villus width in ll the groups. The control group nd glutmine treted groups hd greter increse in jejun villus width t week 4 nd decrese in week 6 nd 8 (Tble 1). The control group lso experienced decrese in ile villus width in week 4 nd 6. Glutmine, honey nd scorbic cid treted groups hd shown sttisticlly significnt increse in villus width (Tbles 2, 3 nd 4) (P<0.05). Ascorbic cid treted group hd lso shown significnt increse in ile villus height. Crypt Depth There ws n increse in crypt depth in ll the groups except the control group (Tbles 15). Glutmine, honey nd glutmine honey nd scorbic cid treted groups cused significnt increse in crypt depth (P<0.05). Ascorbic cid treted nimls significntly enhnced ile crypt depth while the control group did not show ny significnt chnges. Wll thickness All the groups experienced increse in wll thickness except the control group which experience increse only in the ile wll thickness in week 8 of experiment (Tbles 15). Group 2 (glutmine treted), group 3 (honey treted) nd group 5 (glutmine/ honey/ scorbic cid treted) nimls hd shown significnt increse in wll thickness (P< 0.05) Tbles 2, 3 nd 5). Ascorbic cids treted group hd shown significnt increse in jejunl wll thickness (P<0.05) (Tble 4). Tble 1. Jejunl histomorphometric nlysis for dogs (Control group) post 70% smll intestinl resection Jejunum Villus Height (VH) Villus Width (VW) Crypt Depth (CD) WKs Number of dogs (n = 6) Men ±SEM ± ± ± ± ± ± ± ± ± ± ± ± ±0.072 Wll Thickness (WT) ± ± ±0.046 WKs= Weeks; n= Number of dogs P vlue

4 Tble 2. Jejunl histomorphometric nlysis for dogs post 70% smll intestinl resection Jejunum WKs Number of dogs (n = 6) Men ±SEM ±0.037 Villus Height (VH) ± ± ± ±0.161 Villus Width ±0.056 (VW) ± ± \ ±0.039 Crypt Depth ±0.063 (CD) ± ± ±0.058 Wll ±0.092 Thickness (WT) ± ±0.182 WKs= Weeks; n= Number of dogs P vlue Tble 3. Jejunl histomorphometric nlysis for dogs pre nd post 70% smll intestinl resection nd nstomosis Jejunum Villus Height (VH) Villus Width (VW) Crypt Depth (CD) Wll Thickness (WT) WKs WKs= Weeks, n= Number of dog Number of dogs (n = 6) Men ±SEM ±0.074 P vlue ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

5 Tble 4. Jejunl histomorphometric nlysis for dogs pre nd post 70% smll intestinl resection nd nstomosis Jejunum Villus Height (VH) Villus Width (VW) Crypt Depth (CD) WKs Number of dogs (n = 6) Men ±SEM ± ± ± ± ± ± ± ± ± ± ± ± ±0.048 Wll ±0.074 Thickness (WT) ± ±0.049 WKs= Weeks; n= Number of dog P vlue Tble 5. Jejunl histomorphometric nlysis for dogs pre nd post smll intestinl resection nd nstomosis Jejunum Villus Height (VH) Villus Width (VW) Crypt Depth (CD) WKs Number of dogs (n = 6) Men ±SEM ± ± ± ± ±0.006 P vlue ± ± ± ± ± ± ± ±0.053 Wll ±0.038 Thickness (WT) ± ±0.041 WKs= Weeks; n= Number of dog

6 b Figure 1. The jejunum of dogs t eight weeks post resection showing () Necrosis of villi nd (b) leucocytes infiltrtion of lminl propri. (H&E) 100 b Figure 2. The Ileum of dogs t eight weeks post resection showing () mild necrosis nd (b) moderte hyperplsi of villi (H&E)

7 Figure 3. The Jejunum of dogs t eight weeks fter tretment with glutmine showing () formtion of surfce epithelium (H&E) 40 b Figure 4. The ileum of dogs t eight weeks fter tretment with glutmine showing () surfce epithelium (b) Hyperplstic villi (H&E)

8 Figure 5. The Jejunum of dogs t eight weeks fter tretment with honey showing norml villi (H&E) 40 Figure 6. The ileum of dogs t eight weeks fter tretment with honey showing complete recovery (H&E) 40 41

9 Figure 7. The Jejunum of dogs t eight weeks fter tretment with scorbic cid showing leucocytic infiltrtion of lmin propri of the intestinl mucos () (H&E) 100 Figure 8. The ileum of dogs t eight weeks fter tretment with scorbic cid showing thickened lmin propri infiltrted by leucocytes (rrow) (H&E) 40 42

10 Figure 9. The Jejunum of dogs t eight weeks fter tretment showing well formed villi (rrow) (H&E) 40 Figure 10. The Ileum of dogs t eight weeks fter tretment showing well formed surfce epithelium nd villi (rrow) (H&E) 40 43

11 Digrm 1. Preresection nd posttretment jejunl villi height of dogs in control, glutmine, honey, scorbic cid nd glutmine/ honey/ scorbic cid combintion treted groups Digrm 2. Preresection nd posttretment jejun wll thickness of dogs in control, glutmine, honey, scorbic cid nd glutmine/ honey / scorbic cid combintion treted groups Digrm 3. Preresection nd postresection jejunl crypt depth of dogs in control, glutmine, honey, scorbic cid nd glutmine/ honey/scorbic combintion cid treted groups 44

12 DISCUSSION In present study, the effects of glutmine, honey, scorbic cid nd glutmine, honey nd scorbic cid combintion on intestinl dpttion in Nigerin dogs suffering from short bowel syndrome following 70% smll bowel resection ws evluted. Dogs in ll the groups in this study hd dirrhe nd loss of weight which is in greement with the findings of Gormn et l. (2006), Shw et l. (2012) nd Tppenden (2014). The reson ws due to mlbsorption s result of the loss of mucosl bsorptive surfce re ssocited with short bowel syndrome (Shw et l., 2012; CunhMelo nd Cost, 2014; Merritt et l., 2017). However, there ws reduction in dirrhe in nimls treted with glutmine, honey, scorbic cid nd their combintion fter one week of tretment. This is due to the dptive chnges tking plce in the intestinl mucos tht improves bsorption nd digestion of nutrients (Shw et l., 2012; Vgholkr et l., 2016; Gillrd et l., 2017). This is the reson for the increse in weight observed in nimls in these four groups. Animls in the control group however, continue to experience dirrhe especilly fter feeding due to indequte dptive chnges in the intestinl mucosl. Hence the grdul drop in body weight observed in this group. Glutmine is the mjor nutrient for the bowel. It is the primry substrte used by enterocytes. Supplementtion during ctbolic sttes improves structurl integrity, function nd repir of the intestinl mucos, decreses bcteril trnsloction nd epithelil poptosis, improves nitrogen blnce nd influencing gut immune response (Chndler, 2002; Evns et l., 2003; Grimble, 2005; Lrson et l., 2007). Dogs treted with glutmine (group 2) experienced significnt increse (P<0.05) in Villus Height (VH), Crypt Depth (CD), Villus Width (VH) nd Wll Thickness (WT). The grdul increse in body weight observed in this group my be due to enhnced bsorption of nutrients from improved dpttion of the remnnt smll bowel. Our findings on the use of glutmine in this study, grees with the previous work by Eyrefe et l. (2012), who used glutmine on dogs with short bowel syndrome following mssive smll bowel resection nd observed beneficil dptive response by the remnnt smll bowel in those dogs. In this study, dogs treted with honey (group 3) showed significnt increse (P<0.05) in VH, CD, VW nd WT. There ws grdul increse in body weight. There ws lso complete regenertion of the intestinl epithelium. This result is lso in greement with the findings of Eyrefe et l. (2012) who lso used honey to tret dogs suffering from short bowel syndrome nd observed positive dptive response. Dogs treted with scorbic cid showed mrginl increse in VH, VW, CD nd WT. It hs been reported tht mlssimiltion nd incresed fluid losses with dirrhe my deplete vitmin C in the body (Chndler, 2002). It my be possible tht the dosge of vitmin C used in this study ws not enough to compenste for the lrge losses tht hd occurred. Though the increse ws not sttisticlly significnt, it ws comprtively better thn tht of the control group. The ction of scorbic cid (vitmin C) ws s result of its powerful ntioxidnt property where it scvenges nd mopes up rective oxygen nd nitrogen species (free rdicls) in the body. These rective species re generted by norml cell processes s well s environmentl stressors nd cn cuse dmge to tissues (Hlliwell nd White mn, 1997; Telng, 2013). Oxidtive stress lso occurred in the intestine in diseses nd my cuse incresed inflmmtion nd permebility (Chndler, 2002). Thus vitmin C reduced potentil dmge to tissues. All these positive effects my probbly be undermined in this study, due to the insufficiency of vitmin C, which my be responsible for the low/grdul villi height, crypt depth, villi width nd wll thickness. The evlution of scorbic cid in the tretment of short bowel syndrome did not report experimentlly nd there re not enough published dt bout this reserch topic. Dogs on glutmine, honey nd scorbic cid combintion (group 5) showed significnt increse in VH, VW, CD nd WT. This dptive response ws higher thn tht observed in glutmine (group 2), honey (group 3) or scorbic cid (group 4) treted nimls respectively. This showed tht the combintion of these three supplements hd synergistic effect tht could enhnce smll bowel dpttion in ptients with short bowel syndrome. Similrly, the synergistic effect of these products hs not been reported. Animls in the control group did not show ny pprecible dptive response s there ws no significnt increse in VH, VW, CD nd WT. There ws lso drop in body weight. The result of this study hs reveled tht glutmine, honey nd their combintion hve beneficil intestinl dptive response in ptients suffering from short bowel syndrome. However, /glutmine/ honey/ scorbic cid combintion produces higher dptive response thn glutmine, honey or scorbic cid lone. The higher doses of these supplements produced better dptive response thn the lower doses. CONCLUSION Glutmine, honey nd scorbic cid given individully or in combintion enhnced residul bowel efficiency nd improved outcome in ptients suffering from short bowel syndrome. It is therefore recommended tht dogs with signs ttributble to short bowel syndrome should be given supplement of glutmine, honey nd scorbic cid in food. 45

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