Renal functional and structural alterations induced by intramuscular injection of Bothrops leucurus venom

Paloma Santos Hora; Joaquim Roque de Jesus Nogueira Junior; Ricardo David Couto; Leda Maria de Castro Coimbra Campos; Telma de Jesus Soares; Luciana Lyra Casais-E-Silva; Samira Itana de Souza

doi:10.1016/j.toxicon.2023.107265

Renal functional and structural alterations induced by intramuscular injection of Bothrops leucurus venom

Toxicon. 2023 Oct:234:107265. doi: 10.1016/j.toxicon.2023.107265. Epub 2023 Sep 4.

Authors

Paloma Santos Hora¹, Joaquim Roque de Jesus Nogueira Junior², Ricardo David Couto³, Leda Maria de Castro Coimbra Campos⁴, Telma de Jesus Soares¹, Luciana Lyra Casais-E-Silva², Samira Itana de Souza⁵

Affiliations

¹ Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista, Bahia, 45029094, Brazil.
² Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, 40231300, Brazil.
³ Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, 40170115, Brazil.
⁴ Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270901, Brazil.
⁵ Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, 40231300, Brazil. Electronic address: samira.itana@ufba.br.

PMID: 37673342
DOI: 10.1016/j.toxicon.2023.107265

Abstract

Acute kidney injury (AKI) is the main cause of death from Bothrops snakebite. Although many studies have investigated the nephrotoxicity induced by other Bothrops species, no study has assessed the renal alterations induced by intramuscular (i.m.) injection of Bothrops leucurus venom. In this study, we evaluated the nephrotoxicity induced by B. leucurus venom by analyzing renal function and histology. Wistar rats were submitted to i. m. injection of B. leucurus venom or saline and divided into two groups: Control group (C), rats submitted to i. m. injections of saline, and B. leucurus group (Bl), rats submitted to i. m. injections of B. leucurus venom (1 mg/kg). After venom or saline injection, serum and urine were collected to measure creatinine, albumin, sodium, and potassium levels. The glomerular filtration rate (GFR), urinary flow urinary, creatinine/serum creatinine ratio, and albuminuria-urinary creatinine ratio were determined. All rats were euthanized 72 h following the injections, and the kidneys were removed for histology and immunohistochemical studies. B. leucurus experimental envenoming was accompanied by an increase of 236% in serum creatine kinase activity in the Bl group. The weights of the right and left kidneys were, respectively, 26 and 22% higher in rats of the Bl group than in control rats. Regarding renal function, the Bl group showed a decrease of 37% in GFR compared to control group. The rats of the Bl group also presented increased cortical (8.20 ± 1.35) and medullar (6.17 ± 2.00) tubulointerstitial lesion area when compared to control group (0.02 ± 0.00) (1.20 ± 0.73), respectively. The number of macrophages was also higher in the renal cortex (6.66 ± 0.06) and medulla (1.22 ± 0.10) of rats from the Bl group when compared to control rats (1.04 ± 0.55), (0.65 ± 0.10), respectively. Our results indicate that B. leucurus venom promoted significant histological and functional renal alterations following intramuscular inoculation, which simulates the majority of snakebites observed in the clinical practice.

Keywords: Bothrops leucurus; Macrophages; Nephrotoxicity; Renal function; Snakebite.