A histochemical approach to the evaluation of the in vivo cytotoxicity of the nitrobutadienes (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate in mice liver and kidney.
Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.
Fenoglio
C
C
Dipartimento di Biologia Animale, Università di Pavia. P.za Botta 10, 27100 Pavia, Italy. fenoglio@unipv.it
Grosso
A
A
Petrillo
G
G
Boncompagni
E
E
Aiello
C
C
Cordazzo
C
C
Spinelli
D
D
Ognio
E
E
Mariggio
M A
MA
Cassano
A
A
Viale
M
M
D000818:Animals; D015415:Biomarkers; D002070:Butadienes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006651:Histocytochemistry; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D009281:Naphthalenes / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
D015415:Biomarkers; D002070:Butadienes; D009281:Naphthalenes; D017382:Reactive Oxygen Species