Article
Open Access
Changes of pathological and physiological indicators affecting drug metabolism in rats after acute exposure to high altitude
- Authors:
- Wenbin Li
- Rong Wang
- Hua Xie
- Juanhong Zhang
- Zhengping Jia
-
View Affiliations / Copyright
Affiliations:
Department of Pharmacy, Key Laboratory of Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Command, Lanzhou, Gansu 730050, P.R. China
-
Pages:
98-104
|
Published online on:
November 4, 2014
https://doi.org/10.3892/etm.2014.2049
- Expand metrics +
Metrics:
Total
Views: 0
(Spandidos Publications: | PMC Statistics:
)
Metrics:
Total PDF Downloads: 0
(Spandidos Publications: | PMC Statistics:
)
This article is mentioned in:
Abstract
High altitude environments cause the human body to undergo a series of pathological, physiological and biochemical changes, which have a certain effect on drug pharmacokinetics. The objective of the present study was to observe changes in factors affecting pharmacokinetics in rats following acute exposure to high altitude and return to low altitude. A total of 21 male Wistar rats were randomly assigned to three groups. The rats in group A were maintained at low altitude in Shanghai, 55 m above sea level; those in group B were acutely exposed to high altitude in Maqu, Gansu, 4,010 m above sea level; and those in group C were acutely exposed to high altitude and then returned to low altitude. Blood was collected from the orbit for the analysis of significant biochemical indicators and from the abdominal aorta for blood gas analysis. Brain, lung and kidney tissues were removed to observe pathological changes. In group B, the pH, buffer base (BB), base excess (BE), total carbon dioxide content (ctCO2), oxygen saturation of arterial blood (sO2), oxygen tension of arterial blood (pO2), serum sodium (Na+) concentration, lactate dehydrogenase (LDH) activity and total protein (TP) level were significantly reduced, and the carbon dioxide tension of arterial blood (pCO2), serum chloride (Cl-) concentration, serum total bilirubin (TBIL) level and alkaline phosphatase (ALP) activity were significantly increased compared with those in group A (P<0.05). In group C, the pH, BB, BE, sO2, pO2, hemoglobin (Hb) level, serum Na+ concentration, LDH activity and TP level were significantly reduced, and the pCO2, serum Cl- concentration, alanine transaminase activity, TBIL and urea levels were significantly increased (P<0.05) compared with those in group A. The Hb and ALP levels in group C were significantly lower than those in group B (P<0.05); and the TP, TBIL and urea levels in group C were significantly higher than those in group B (P<0.05). Pathological observation revealed that the alveolar wall was hyperemic, edematous and incrassate, the alveolar epithelium was hyperplastic and infiltrated with neutrophilic granulocytes and the alveolar septum was widened; brain neurons were edematous with enlarged perivascular spaces, and hippocampal neurons were metamorphic and karyopyknotic; and kidney mesangial cells were hyperplastic, both following acute exposure to high altitude and after returning to low altitude. In conclusion, blood gas indices, biochemical indicators and functions of the heart, liver, kidney were significantly changed, and marked pathological changes occurred in the brain, liver and kidney following acute exposure to high altitude and also after returning to low altitude. These changes are likely to seriously affect the pharmacokinetics of drugs.
View Figures |
Figure 1
|
 |
Figure 2
|
 |
Figure 3
|
 |
Figure 4
|
 |
Figure 5
|
 |
Figure 6
|
 |
Figure 7
|
 |
Figure 8
|
 |
Figure 9
|
 |
Figure 10
|
 |
Figure 11
|
 |
Figure 12
|
View References
|
1
|
Zhao H, Chai W, Gao W, Xu L, Zhang H and
Yang Y: Hyperoxygenated solution: effects on acute hypobaric
hypoxia-induced oxidative damage in rabbits. High Alt Med Biol.
10:283–291. 2009. View Article : Google Scholar : PubMed/NCBI
|
|
2
|
Donovan L, Welford SM, Haaga J, LaManna J
and Strohl KP: Hypoxia - implications for pharmaceutical
developments. Sleep Breath. 14:291–298. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Brenner GM and Stevens CW: Pharmacology.
4th Edition. Elsevier; Philadelphia, PA, USA: 2012
|
|
4
|
Jun F, Jun Q, Chun-xia L, et al:
Establishment of normal reference range of blood hematological and
biochemical indicators of SPF wistar rats. Gonggong Weisheng Yu
Yufang Zazhi. 21:50–52. 2010.(In Chinese).
|
|
5
|
Grenache DG and Parker C: Integrated and
automatic mixing of whole blood: an evaluation of a novel blood gas
analyzer. Clin Chim Acta. 375:153–157. 2007. View Article : Google Scholar
|
|
6
|
Mahutte CK: On-line arterial blood gas
analysis with optodes: current status. Clinical Bioch. 31:119–130.
1998. View Article : Google Scholar
|
|
7
|
Venkatesh B and Boots RJ: Carbon dioxide
and oxygen partial pressure measurements in the cerebrospinal fluid
in a conventional blood gas analyzer: analysis of bias and
precision. J Neurol Sci. 147:5–8. 1997. View Article : Google Scholar : PubMed/NCBI
|
|
8
|
Mitra A and Kesisoglou F: Impaired drug
absorption due to high stomach pH: a review of strategies for
mitigation of such effect to enable pharmaceutical product
development. Mol Pharm. 10:3970–3979. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Wang JF, Guo ZJ, Huang HQ, et al:
Correlation between hemoglobin and mountain response after rapidly
ascended to highlands in different periods. Journal of Qinghai
Medical College. 31:184–186. 2010.(In Chinese).
|
|
10
|
Karinen HM, Peltonen JE, Kähönen M and
Tikkanen HO: Prediction of acute mountain sickness by monitoring
arterial oxygen saturation during ascent. High Alt Med Biol.
11:325–332. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
11
|
Gao F, Feng XY and Du FM: Effects of blood
glucose, lipid and dielectric on SMZCo pharmacokinetics after
short- and long-time exposure to high-altitude. Chinese Journal of
Modern Applied Pharmacy. 27:239–242. 2010.(In Chinese).
|
|
12
|
Liu RW: Modern Clinical Laboratary
Diagnostics. Chemical Industry Press; Beijing: pp. 99–123. 2009
|
|
13
|
Mei D, Xu B, Sun K, Wang LH and Zhang W:
Changes of serum biochemical parameters during hypothermia and
hypoxia in rats. Space Med Med Eng (Beijing). 12:274–276. 1999.(In
Chinese).
|
|
14
|
Dai Y, Dai DJ, Wang Z and Ren Q: Effect of
acute hypobaric hypoxia on renal function and structure in rats.
Space Med Med Eng (Beijing). 3:215–217. 2000.(In Chinese).
|
|
15
|
Li SZ: Hypoxia height dependability
disease in high altitude and discussion of new mountain sickness.
Medical Journal of National Defending Forces in Southwest China.
21:336–338. 2011.(In Chinese).
|
|
16
|
Grocott M, Montgomery H and Vercueil A:
High-altitude physiology and pathophysiology: implications and
relevance for intensive care medicine. Crit Care. 11:2032007.
View Article : Google Scholar : PubMed/NCBI
|
|
17
|
Bito LZ: Prostaglandins and other
eicosanoids: their ocular transport, pharmacokinetics, and
therapeutic effects. Trans Ophthalmol Soc U K. 105:162–170.
1986.PubMed/NCBI
|
