Clinical communication — Kliniese mededeling

Hyperzincaemia in a pet African giant rat (Cricetomys gambianus Waterhouse, 1840)

R G Coopera* and K H Erlwangerb

determinations were made by spectro- ABSTRACT photometric analysis38. Red blood cells Presented is an African giant rat (Cricetomys gambianus) following zinc ingestion. The sick (RBC) and white blood cells (WBC) were rat was lethargic, withdrawn, had soft, mucus-impregnated faeces and diahorrea, foot counted with a haemocytometer (Gilson twitching and icterus. Comparative age, sex and body weight (b.wt.)-matched analyses Microman, Anachem, UK), and blood were made with a healthy giant rat. Twelve-hourly Urine volume (UV), Haematocrit (Hct), smears were stained with Giemsa stain urinary glucose, plasma zinc and Alkaline Phosphatase (ALP) were performed over an for differential leukocyte counts25. Optical 8-week period. Full blood counts were performed and differential WBC counts and micro- microscopic observations of RBC were scopic observations were made on blood smears obtained from both healthy and sick rats. Consecutive blood samples were drawn at the end of each week (Weeks <2–6 treatment; made at ×400 magnification. Alkaline Weeks 7–8 post-treatment). Treatment involved oral vitamin B12 supplement at 4 µg/day phosphatase (ALP) was measured with a ® and 2 m diethylenetriaminepentaacetic acid (DTPA) intramuscular injections at 1 m /450g kit (Telechem International Inc., ArrayIt b.wt./5 wks (Week 2 – 6). Day 1 showed neutropaenia, Heinz bodies on RBCs (reticulocytes Division, Sunnyvale, USA). The assay and immature forms). Zinc (Day 1 – end Week7), glucose (Day 1 – end Week4), ALP (Day 1 – used quantitative colorimetric analysis on Week 4) and UV were elevated (Day 1 – end Week 6). Indications of moderate zinc toxicosis sample sizes of 200 µ . The test was based following ingestion and stress-associated glucosuria were concluded. on the conversion of para-nitrophenyl- Key words: African giant rat, Cricetomys gambianus, glucosuria, gnawing, hyperzincaemia, pet. phosphate (p-NPP) to para-nitrophenol Cooper R G, Erlwanger K H Hyperzincaemia in a pet African giant rat (Cricetomys and the colorimetric determination of gambianus Waterhouse, 1840). Journal of the South African Veterinary Association (2007) 78(3): the resulting coloured product. The test 163–165 (En.). Division of Physiology, UCE Birmingham, 701 Baker Building, Franchise system was optimised with respect to Street, Perry Barr, Birmingham B42 2SU, UK. substrate concentration, and reaction time. The obtained values were converted to quantitative results through a standard curve created using commercial ALP. INTRODUCTION poisoned by chronic ingestion of zinc Consecutive blood samples were collected The African giant rat or the Gambian from gnawing activity on a cage. every 7 days after Day 1 over a 7-week pouched rat, Cricetomys gambianus (Order: period subdivided into Week 2–6 treat- Rodentia; Family: Nesomyidae) is the MATERIALS AND METHODS ment and Week 7–8 post-treatment world’s largest nocturnal rat and is native The sick giant rat was housed in the 1,7 periods (Table 1). Treatment was admin- to Africa, many thriving in urban settings . Animal house at West Bar Veterinary istered 1 hour following diagnosis. The They live up to 8 years in captivity reach- Hospital, Banbury, UK (temperature diagnosis was made 2 days following the ing maximum body weights of approxi- 23 °C; RH 37 %; 24 h light/24 h dark cycle). onset of sickness. Treatment included vi- mately 2.8 kg in bucks and 1.39 kg in does. The healthy rat was housed in a North 11 tamin B12 supplement orally at 4 µg/day They have become extremely popular as Kent Plastics (NKP) metabolism cage, and 2 m diethylenetriaminepentaacetic exotic pets and are used to detect land- Dartford, Kent, UK. Food, including 9 mines. Field observations and notes on Mouse Comproids, boiled chicken, vege- acid (DTPA) injections administered the behaviour and domestication of this tables, and water were provided ad libi- intramuscularly at a dose of 1 m /450 g rat have been published1–3,6. tum. The healthy rat was only used to b.wt. for 5 weeks (Week 2–6). Vitamin B12 Chronic zinc ingestion has been reported compare initial basal values at diagnosis. was administered to stimulate erythro- to cause copper deficiency and anaemia Due to expense of rats and ethics, only 2 poeisis and as a hepatic stimulant for pro- 36 as a consequence of the intestinal interac- rats were observed in the current study. cessing haemoglobin . An extensive tion of zinc and copper34. Acute zinc Urine volume presented as mean ± stan- search of the literature revealed 3 studies poisoning is reflected in a haemolytic dard error of the mean (s.e.m.) was deter- on the haematological parameters of the 10,20,26 crisis with renal, gastrointestinal and mined from 12-hour collections over an giant rat . Results from these studies hepatic dysfunction37. 8-week period. Day 1 was taken as the day were used to establish the normal param- This is a case report of a 2-year,9-month- of diagnosis. A venous tail blood sample eters of haematology in the current inves- old female pouched rat (897.21 g b.wt.) (1 m ) was collected (Day 1, Table 1), tigation. Handling and experimentation cooled in a heparinised tube, centrifuged were in strict accordance with the stipula- aDepartment of Physiology, College of Health Sciences, University of Zimbabwe, Mount Pleasant, Harare, Zimba- at 10 000 rpm and subjected for haemato- tions in Animals (Scientific Procedures) bwe. logical and biochemical analyses. Haema- Act of 1986 (UK). There was no need for an bSchool of Physiology, Faculty of Health Sciences, Univer- ethics approval protocol as the study was sity of the Witwatersrand, Parktown 2193, South Africa. tocrit (Hct) was determined by micro- *Author for correspondence. Present address: Division centrifugation, a 2-Drop Clinitest (Bayer a clinical case report. All data were com- of Physiology, UCE Birmingham, 701 Baker Building, Diagnostic) with glucose sensitivity accu- pared between sick rat and healthy rat, Franchise Street, Perry Barr, Birmingham B42 2SU, UK. E-mail: [email protected] rate over 1 g/ was used for urinary glu- and, where appropriate, acceptable refer- 11,39 Received: July 2007. Accepted: September 2007. cose determination and plasma zinc ence intervals were considered.

0038-2809 Jl S.Afr.vet.Ass. (2007) 78(3): 163–165 163 Table 1: Biochemical, haematological and fluid balance parameters measured at the end of each week in an African giant rat chronically exposed to zinc during treatment over 6 weeks with vitamin B12 and DTPA, and a 2-week post-treatment period.

Parameter Treatment at the end of the week Post-treatment Day 1 (Week 1) Week 2 Week 3 Week 4 Week 5 Week6 Week 7 Week 8 Zn2+ (67.0 µ g/100m ) a 172.8* 165.6* 134.3* 126.6* 103.9* 98.1* 82.0* 70.0 Urinary glucose (0.0 g/ ) 4.2* 1.7* 1.4* 1.1* 0000 ALP (79.0 UI/ ) 133.0* 120.0* 101.0* 90.0* 82.0 80.0 79.0 79.0 Hct (40.0%) 31.0* 32.0* 34.0* 38.5 40.0 40.0 40.0 40.0 Mean (sem) UV (6 ± 1 m /h) 12 (1)* 14 (2)* 13 (1)* 12 (2)* 10 (1)* 9 (2)* 6 (2) 5.8 (2) aBaseline value obtained from a healthy rat. *Comparative differences between healthy and sick rats. RESULTS coated cage, urinary glucose was attenu- previous study21. The sick rat had clearly Approximate b.wt. were 897.21 g for the ated to 1.7 g/ at the end of Week 2 consumed more that the recommended sick rat and 908.32 g for the healthy rat. (Table 1). Urinary glucose concentrations dietary allowance of 15 mg Zn/d in hu- Initial observations of the sick rat showed progressively decreased over subsequent mans12. Species-specific pharmacokinetic that it was lethargic, withdrawn and weeks reaching 0 g/ at the end of Week 5 properties of Zn in giant rats is unknown. passing soft, mucus-impregnated faeces (Table 1). ALP was increased up to the end Indeed, high Zn levels could be either due interspersed with diahorrea. Foot twitch- of Week 4 (Table 1). Hct remained attenu- to high daily intake of Zn or accumulative ing and icterus were observed in the hind ated up to the end of Week 3 (Table 1). effects of the ion. Icterus has been re- legs and mouth, respectively. The rat had Urine volume, although greater than ported in cases of zinc intoxication in been anorexic for 3 days. The urine was healthy value, decreased steadily, reach- dogs16,23. The yellow mucus membranes not discoloured. Where appropriate, values ing a value by the end of Week 7 that characteristic of icterus may be a conse- were presented in comparison with mini- did not differ from the healthy value quence of extra-vascular haemolysis. mum and maximum values, and a refer- (Table 1). Microscopic analysis demonstrated the ence value from previous haematological existence of Heinz bodies in RBC, a investigations in this species. DISCUSSION well-known side effect of zinc toxicity16. Haematological analyses on Day 1 Giant rats are one example of an exotic The presence of immature RBCs was in- demonstrated an anaemia with a RBC pet. They are less commonly kept that the dicative of regenerative anaemia. The count of 4.95 × 109/ (reference interval: domestic albino rat, principally due to anaemia, however, had not progressed 5.5–11.0 × 109/ ) by comparison with lack of knowledge of this species amongst into sideroblastic4,30 or hypocupremia previous findings of 5.49 × 109/ 26;an buyers and expense at purchase8. As such, anaemia30 suggesting a moderate expo- attenuated WBC count of 4.20 × 109/ although this clinical case appears due to sure to zinc. Neutropaenia, as a result of (reference interval: 5.5–11.0 × 109/ ) a low-incidence toxicity, it is essential that zinc toxicosis, has been confirmed in pre- compared with previous findings of it is reported for small animal veterinary vious investigations4,21,35. We suggest that 6.64 × 109/ 26; and lymphocytes with a knowledge. We deduced that the sick rat zinc interferes with the development of value of 5.53 × 109/ (reference interval: was suffering from a combination of zinc formed neutrophils in bone marrow by 4.0–6.3 × 109/ ) compared with. 4.63 × toxicity and stress-induced glucosuria. disrupting metabolic reactions in commit- 109/ 26. The proportion of neutrophils Poisoning from zinc was due to the rat’s ted stem cells. No evidence of infection at Day 1 was reduced to 0.92 × 109/ cage being made of galvanised steel on was concluded as there was no left shift in (reference interval: 1.02–3.87 × 109/ )by which it gnawed. Giant rats commonly or production of immature white blood comparison with 1.13 × 109/ 26. There knaw at their cages and inclusions cells. were Heinz bodies present on numerous therein; this behaviour is neither associ- Urinary excretion of zinc is increased in RBC and there were many immature RBC ated with explorative nor with supporta- human patients with Type 1 diabetes (reticulocytes and immature forms). tive activity when climbing within the mellitus5. It is probable that although Zinc and glucose concentrations on cage8. It may have been probable that the there is a positive correlation of mean Day 1 were increased at 172.8 (sick) vs. 67 gnawing activity was a consequence of fasting plasma zinc, duration of diabetes (healthy) µ g/100 m and 4.2 g/ (1.7 g/ inadequate housing, but this was not and glucose excretion11,31, the glucosuria min.; 3.3 g/ max.) vs 0g/ , respectively (Ta- investigated in the current study. It was observed in our study was not linked to ble 1). ALP concentrations in the sick rats noted that the rat in question was kept in the hyperzincaemia. Diabetes certainly were elevated at 133 UI/L (37 °C) (refer- isolation in its cage. It is possible that elevates plasma ALP levels24,33. The normal ence interval: 15–85 UI/ ) by comparison the glucosuria was a consequence of zinc range of ALP was in close agreement with a healthy value of 79 UI/ of the rat in toxicity resulting in renal damage. We with studies in other animals19,29.The our study (Table 1). Hct at Day 1 was low suggested that chronic zinc exposure attenuated ALP levels from Day 1 to the at 31 % vs 40 % in the healthy rat (Table 1). manifested itself sympathetically in end of Week 4 were commensurate with a Urine volume was elevated on Day 1 muscle twitching possibly through stimu- declining urinary glucose concentration, (Table 1). Results from Day 1 prompted, lated release of neurotransmitters. Allied, suggesting transitory hyperglycaemia. at the time, possible diagnoses of zinc albeit contradictory studies, have demon- We suggest that due to excessive stress, toxicity, hyperglycaemia, or glucosuria as strated that zinc stimulates spontaneous the sick rat developed transitory hyper- a consequence of renal damage. release at neuromuscular junctions17,18,28 glycaemia with glucose spilling into the Plasma zinc concentrations were ele- and inhibits the entry of calcium into urine resulting in the observed glucosuria. vated from Day 1 until the end of Week 7, nerve terminals thereby inhibiting trans- Indication of such has been described in thereafter reaching values that did not mitter release27. Plasma concentration of other studies15,34. However, in the absence differ from the healthy values (Table 1). zinc in the healthy rat at Day 1 in this of blood glucose determinations, these Following source removal, i.e. the zinc- study lay within ranges reported in a deductions can only be considered specu-

164 0038-2809 Tydskr.S.Afr.vet.Ver. (2007) 78(3): 163–165 lative. As these rats were not sacrificed and Tobago Field Naturalists’ Club: 54–55 poisoning in a dog. Veterinary and Human due to expense, it was impractical to draw 3. Ajayi S, Tewe O, Faturoti E 1978 Behavioral Toxicology 46(5): 272–275 changes in African giant rat (Cricetomys 23 Broun E R, Greist A, Tricot G, Hoffman R blood for glucose determinations as this gambianus Waterhouse) under domestica- 1991 Excessive zinc ingestion. A reversible may have adversely influence the health tion. East African Wildlife Journal 16(2): cause of sideroblastic anemia and bone of the animals. Indeed, the 1 m of blood 137–143 marrow depression. The Journal of the drawn for haematological and biochemical 4. Cooper R G 2000 Giant rat in Zimbabwe. American Medical Association 265(7): 869 Rat & Mouse Gazette 6(1): 26 24. Porea T J, Belmont J W,MahoneyDHJr2000 analysis was insufficient for glucose 5. 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