TABLE 1

No evidence for liver, kidney, or heart toxicity following up to 10 days of treatment

BL/6 (no treatment)BL/6 + STZBL/6 + STZ + zVAD (10 days' treatment)BALB (no treatment)BALB + STZBALB/C + STZ + zVAD (5 days' treatment)
Kidney function       
    Blood urea nitroge (mmol/l) 14.73 ± 3.59 12.30 ± 0.53 11.33 ± 0.12 8.03 ± 0.09 6.65 ± 0.15 5.90 ± 1.9 
    Creatinine (umol/l) 27.67 ± 3.18 12.33 ± 1.45 19.33 ± 0.88 13.33 ± 2.40 — — 
Liver function       
    Alkaline phophatase (IU/l) 138.00 ± 18.82 200.00 ± 5.03 192.67 ± 2.03 132.00 ± 4.04 124.00 ± 14.00 119.00 ± 20.0 
    Alanine aminotransferase (IU/l) 51.00 ± 8.51 51.00 ± 2.31 49.00 ± 0.00 41.33 ± 1.45 79.50 ± 1.50 72.00 ± 1.0 
    γ-Glutamyltransferase (IU/l) 12.00 ± 3.61 9.00 ± 1.73 6.67 ± 0.88 6.33 ± 1.20 9.50 ± 0.50 6.00 ± 6.0 
Cardiac function       
    Creatine phosphokinase (IU/l) 334.33 ± 87.23 285.33 ± 9.82 187.67 ± 13.37 253.67 ± 10.84 308.50 ± 33.50 195.50 ± 73.5 
BL/6 (no treatment)BL/6 + STZBL/6 + STZ + zVAD (10 days' treatment)BALB (no treatment)BALB + STZBALB/C + STZ + zVAD (5 days' treatment)
Kidney function       
    Blood urea nitroge (mmol/l) 14.73 ± 3.59 12.30 ± 0.53 11.33 ± 0.12 8.03 ± 0.09 6.65 ± 0.15 5.90 ± 1.9 
    Creatinine (umol/l) 27.67 ± 3.18 12.33 ± 1.45 19.33 ± 0.88 13.33 ± 2.40 — — 
Liver function       
    Alkaline phophatase (IU/l) 138.00 ± 18.82 200.00 ± 5.03 192.67 ± 2.03 132.00 ± 4.04 124.00 ± 14.00 119.00 ± 20.0 
    Alanine aminotransferase (IU/l) 51.00 ± 8.51 51.00 ± 2.31 49.00 ± 0.00 41.33 ± 1.45 79.50 ± 1.50 72.00 ± 1.0 
    γ-Glutamyltransferase (IU/l) 12.00 ± 3.61 9.00 ± 1.73 6.67 ± 0.88 6.33 ± 1.20 9.50 ± 0.50 6.00 ± 6.0 
Cardiac function       
    Creatine phosphokinase (IU/l) 334.33 ± 87.23 285.33 ± 9.82 187.67 ± 13.37 253.67 ± 10.84 308.50 ± 33.50 195.50 ± 73.5 

Sera was collected from two strains of mice (BALB/C and C57BL/6) and analyzed after no treatment, streptozotocin administration, and streptozototin administration followed by zVAD treatment for up to 10 days. Renal function was evaluated using blood urea nitrogen and creatinine. Liver function was evaluated using alkaline phophatase, alanine aminotransferase, and γ-glutamyltransferase. Creatine phosphokinase was used as an indicator of cardiac muscle damage. Creatinine levels were significantly higher in zVAD-treated STZ-C57BL/6 mice compared with STZ-C57BL/6 control animals, suggesting that zVAD can prevent nephrotoxicity (P = 0.015). No significant difference was observed for any other values after zVAD treatment in either strain, compared with streptozotocin alone or no treatment. These data are representative of n = 5 animals per cohort.

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