Impact of early malnourishment on the chronic inflammatory response and its implications for the effect of indomethacin on Wistar rats

Abstract

The objective of the present study was to investigate whether early undernutrition changes the chronic inflammatory response, so as to study its influence on pharmacological response to indomethacin. Rat offspring of dams fed from the first day of gestation to term or throughout the lactation period received a balanced diet (NN) or a basic regional diet (BRD) from northeast Brazil. According to their dams, the offspring were divided into three groups: NN; basic regional diet during gestation (BRD-g, undernourished during gestation); basic regional diet during gestation and lactation (BRD-gl, undernourished during gestation and lactation). At 2 months of age, Freund's adjuvant (0·2 ml) was inoculated into the plantar surface of the hind paw (day 0) of animals. All animals orally received saline (0·9 %) for 28 d. Another group of adult offspring was subjected to the same procedure as described above, but orally received indomethacin (2 mg/kg) instead of saline, and divided into three subgroups: NN treated with indomethacin (NNI); BRD-g treated with indomethacin (BRDI-g); BRD-gl treated with indomethacin (BRDI-gl). The hind paw volume was calculated on days 0 (initial paw volume), 7, 14 and 28. Hind paw swelling, blood albumin and C-reactive protein (CRP) levels and leucocyte counts were evaluated as markers of inflammation. Reduced hind paw swelling and the blood levels of serum albumin and CRP were found in the BRD-g and BRD-gl offspring. However, no difference was found in the leucocyte count. Compared with their respective saline-treated groups (NN, BRD-g and BRD-gl), the anti-inflammatory effect of indomethacin was lower in the BRDI-g and BRDI-gl groups than in the NNI group. We conclude that early undernutrition attenuated the chronic inflammatory response and the anti-inflammatory effect of indomethacin.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

“…A recent study by de Oliveira Assis and colleagues reports that administration of the RBD during gestation and lactation to dams was associated with a reduced systemic inflammatory response in the offspring [29], suggesting that the timing and degree of intestinal maturation, change in diets, and intestinal milieu play a role in modulating intestinal inflammatory responses.…”

Furosemide Pharmacokinetics in Adult Rats become Abnormal with an Adverse Intrauterine Environment and Modulated by a Post‐Weaning High‐Fat Diet

“…This process is called the ‘developmental origins of health and disease’ . Previous reports have associated IUGR with altered diminished drug responses; these include blood pressure and diuresis with antihypertensive agents, hexobarbital‐induced sleep time, and indomethacin anti‐inflammatory response .…”

“…One of the few and most prescient clinical observations with respect to pharmacotherapy was made by Lackland et al . in a study of antihypertensive use in the south‐eastern United States . They observed that low‐birthweight black women were more likely to receive calcium channel antagonists and white men of low and high birthweights were more likely to be treated with angiotensin‐converting enzyme inhibitors.…”

“…This process is called the 'developmental origins of health and disease' [2]. Previous reports have associated IUGR with altered diminished drug responses; these include blood pressure and diuresis with antihypertensive agents, hexobarbital-induced sleep time, and indomethacin anti-inflammatory response [8,21,22]. One of the few and most prescient clinical observations with respect to pharmacotherapy was made by Lackland et al in a study of antihypertensive use in the south-eastern United States [8,21,22].…”

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study

“…It is interesting to note, that indomethacin tends to lower serum albumin, even without infection. As 90-99% of indomethacin is bound to albumin in the bloodstream, reduced albumin levels lead to an increased concentration of free indomethacin, and thus an even worse antibacterial activity during infection [21]. …”