Induction of acute phase reaction and suppression of the immune system in the paraoxon-intoxicated rats

Abstract

Widespread use of organophosphates, especially in agriculture, led us to study their toxic effects. Our investigations were focused on paraoxon an oxygenated analog of a phosphothionate pesticide. This points to an analogy between the response to organophosphate intoxication and the acute phase reaction to injury. The capacity of paraoxon to elicit the acute phase response was assessed by studying two major processes characteristic of acute inflammation, the expression of acute phase proteins (APP) and the immunosuppressive activity of serum. After an LDso paraoxon administration to rats, the serum APP levels increased with time reaching a maximal level at the 24 h time point. The several-fold increases of AGP, MG, Hp and TST concentrations in the circulation of intoxicated rats, as well as a significant immunosuppressive activity of examined animal serum, pointed to the role of APP, especially AGP and MG, as immune modulators. These processes are analog to those observed during the acute phase response to injury and aimed at reestablishing homeostasis.Široka upotreba organofosfatnih jedinjenja u industriji, a posebno u poljoprivredi, navela nas je da ispitujemo njihove toksične efekte. Istraživanja su bila fokusirana ka paraoksonu, kiseoničnom analogu fosfotionatnog pesticida, sa ciljem da se utvrdi analogija između odgovora organizma na intoksikaciju paraoksonom i akutno fazne reakcije na povredu. Sposobnost paraoksona da indukuje akutno fazni odgovor analizirana je ispitivanjem dva glavna procesa karakteristična za inflamaciju: ekspresije akutno faznih proteina i imunosupresivne aktivnosti seruma. Nakon ubrizgavanja LDso paraoksona u pacove, nivo akutno faznih proteina u serumu životinja se povećava dostižući maksimalni nivo u 24 satu. Višestruko povećanje koncentracije al- kiselog glikoproteina (AGP), a2-makroglobulina (MG), haptoglobina i tiostatina u cirkulaciji tretiranih pacova kao i značajna imunosupresivna aktivnost seruma tretiranih životinja ukazali su na ulogu ovih proteina, naročito AGP i MG, kao finih modulatora imunološkog odgovora. Ovi procesi su analogni procesima tokom akutno faznog odgovora organizma na povredu i odvijaju se u cilju uspostavljanja fiziološke ravnoteže.nul