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Lab Anim. 2019 Jan 24:23677218824382. doi: 10.1177/0023677218824382. [Epub ahead of print]

Retrobulbar Sinus Injection of Doxorubicin is More Efficient Than Lateral Tail Vein Injection at Inducing Experimental Nephrotic Syndrome in Mice: A Pilot Study.

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1 Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Germany.
2 Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich, Eberhard Karls University Tübingen, Germany.
3 German Centre for Diabetes Research (DZD), Eberhard Karls University Tübingen, Germany.
4 Werner Siemens Imaging Centre, Eberhard Karls University Tübingen, Germany.
5 Institute of Veterinary Pathology, Ludwig-Maximilians-University, Germany.
6 Facility for Animal Welfare, Veterinary Service and Laboratory Animal Science, Eberhard Karls University of Tübingen, Germany.


Doxorubicin-induced nephropathy in mice is a model for studying experimental nephrotic syndrome. It corresponds to puromycin aminonucleoside nephrosis in rats. In this model, susceptible 129 S1/SvImJ mice are administered a rapid intravenous injection that can be accomplished via either the lateral tail vein or the retrobulbar sinus. Because doxorubicin is a highly toxic substance, extravasation must be avoided during the administration of the intravenous injection to prevent the development of large necrotizing lesions and exacerbation of the animals' stress. In the present study, we compared the safety and stress of these two injection routes by using histopathological analyses of the animals' orbital cavities or tails, respectively. The injection of 14.5 µg/g body weight doxorubicin into the mice's lateral tail veins ( n = 9) or retrobulbar sinuses ( n = 19) caused no clinically detectable stress or impairment. Histopathologies of the specimens five days after doxorubicin injection revealed inflammatory lesions at the injection sites in both groups. In the orbital sinus specimens from the retrobulbar-injected group, fibrosis was evident 25 days after injection. Moreover, while all of the retrobulbar-injected mice (100%) developed nephrotic syndrome, tail vein-injected mice had a significantly lower response rate (66%, p = 0.047, Fisher's exact test) and exhibited only attenuated features of nephrotic syndrome. It was therefore concluded that doxorubicin administration via either lateral tail vein or retrobulbar sinus injections led to a similar induction of histopathological changes with no effects on the clinical well-being of the mice. However, retrobulbar sinus injections were more efficient for inducing experimental nephrotic syndrome.


3R; doxorubicin; experimental nephrotic syndrome; lateral tail vein injection; mice; refinement; retrobulbar sinus injection


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