Co esponding au ho : Allison Theodo e A hanasius.
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
His ological based sub-ch onic oxici y es ing o a ge hea y me als o c ude oil spill;
Using he his o-mo phome y o li e o Wis a a
Allison Theodo e A hanasius 1, * and Ogoun Timipa Richa d 2
1 Depa men o Ana omy, Facul y o Basic Medical Sciences, College o Heal h Sciences, Uni e si y o Po Ha cou , Nige ia.
2 Depa men o Ana omy, Facul y o Basic Medical Sciences, Bayelsa Medical Uni e si y, Nige ia.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 26(02), 2590-2598
Publica ion his o y: Recei ed on 28 Ma ch 2025; e ised on 09 May 2025; accep ed on 11 May 2025
A icle DOI: h ps://doi.o g/10.30574/wja .2025.26.2.1704
Abs ac
This s udy was aimed o e alua e in his ological e m, he suc-ch onic oxici y o some a ge c ude oil con aminan s on
he his o-mo phome y o he li e o exposed Wis a a s. The ollowing a ge chemicals (TCs; cadmium (Cd),
ch omium (C ), coppe (Cu), lead (Pb) and nickel (Ni) we e selec ed based on indings om li e a u e e iew o chemical
analysis done on c ude oil spill si e. Thi y (30) inb ed male Wis a a s o a e age weigh 150-200g (5 o con ol and
25 o expe imen al – 5 o each o he i e TC ea ed g oups). Ra s we e la e sac i iced and he a ge o gan (li e )
excised and used o quali a i e his ological e alua ion. G oss ana omical assessmen showed ha he e was no
signi ican di e ence (P> 0.05) when co ela ing weigh gain be ween he ea ed and con ol g oups. His ological
e alua ion showed he ollowing majo lesions: glome ula conges ion, degene a ion and nec osis; ubula
degene a ion and nec osis; In e s i ial in lamma ion, hemo hage and nec osis. This s udy gi es c edence o he ac
ha his ology-based e idence is a e i able ool o assessing suble hal le el o en i onmen al s esso s in he
ce i ica ion o oxici y.
Keywo ds: Wis a Ra ; Li e ; His ology; Sub-Ch onic Toxici y; Toxici y; Hea y Me als
1. In oduc ion
Toxicology is a b anch o biology, chemis y, and medicine (mo e speci ically pha macology) conce ned wi h he s udy
o he ad e se e ec s o chemicals on li ing o ganism (Sch age , 2006). I also s udies he ha m ul e ec s o chemical,
biological and physical agen s in biological sys em ha es ablishes he ex en o damage in li ing o ganisms. The
ela ionship be ween dose and i s e ec s on he exposed o ganism is o high signi icance in oxicology. Fac o s ha
in luence chemical oxici y includes; he dosage (and whe he i is acu e o ch onic), he ou e o exposu e, he species,
age, sex and en i onmen .
Toxici y es s can measu e le hal and/o suble hal e ec s. These e ec s a e known as measu emen endpoin s: ha is,
hey a e ecological a ibu es ha may be ad e sely a ec ed by exposu e o si e con aminan s ha a e eadily
measu able. In addi ion, each measu emen endpoin is closely ela ed o an assessmen endpoin . Because o his close
ela ionship, a measu emen endpoin can app oxima e o ep esen he assessmen endpoin i he assessmen
endpoin is no amenable o di ec measu emen (USEPA, 1992). Based on he measu ed end poin s, oxici y es ing can
be di ided in o acu e oxici y es ing, sub-ch onic oxici y es ing and ch onic oxici y es ing. Sub-ch onic oxici y
es ing was applied o his s udy, which is de ined as a p olonged oxici y es o 14 day. This p olonged oxici y es
may be used in place o he acu e oxici y es i a longe obse a ion pe iod is conside ed app op ia e (OECD, 1984),
o example i es ing highly lipophilic, poo ly wa e -soluble subs ances, and/o he epo ing o addi ional in o ma ion
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 26(02), 2590-2598
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is conside ed necessa y. The p inciple o he es is ha h eshold le els o le hal and o he obse ed e ec s and NOEC
a e de e mined a in e als du ing he es pe iod (OECD, 1992a).
O ganism exposu e o haza dous chemicals causes inc ease in he le els o s ess p o eins, which induces speci ic
de oxi ica ion sys em esponses, e lec ing hei compensa o y po en ial. When hese sys ems a e o e whelmed, i
causes suble hal e ec which usually begins as biochemical al e a ions a he molecula le els o biological o ganiza ion.
This change migh no impai cellula unc ion un il when i esul s in he o ma ion o a lesion, which is any s uc u al
damage o al e a ions in an o gan, issue o cell o an o ganism due o an inju ious s imulus. Lesion diagnosis is a epo
on he quali a i e and/o quan i a i e g oss mo phological al e a ions o o gans o his o-mo phological al e a ion o
issues, cells and o ganelles, including he his o-chemical changes ha occu a he molecula le el o biological
o ganiza ion. Diagnos ic s a emen o a lesion is based on he p edominan lesion(s) in he issue, while lesion
desc ip ion can be based on he se e i y (mild mode a e o se e e), dis ibu ion ( ocal, mul i- ocal o di use), loca ion
(in acellula , epi helial o in e s i ial) and pa hogenesis (adap i e degene a i e, in lamma o y, and neoplas ic). In so
a ha suble hal lesions o oxic subs ances is insidious and usually begins a he subcellula le els o biological
o ganiza ion, e en be o e i s mani es a ion o impai men o he physiology o he a ec ed cell, his ology as an
assessmen ool is he e o e a gold s anda d in ce i ica ion o oxici y – in a labo a o y oxicological se ing o pollu ion
in an eco oxicological se ing. I is no ewo hy ha physiologic and biochemical changes a e p edominan ly due o
s uc u al abno mali y o issue which his opa hology in es iga es. Hence, lesion diagnosis is a gold s anda d in
diagnosis o disease pa hogenesis and pa hognomonic his opa hologic ea u es. Some lesions a e pa hognomonic
his opa hological ea u es ha a e speci ically dis inc i e o cha ac e is ic o some diseases o pa hological condi ions.
The li e is unique in ha i ecei es blood om wo sou ces: he hepa ic a e y and he po al ein. As hese essels
en e he li e , hei e minal b anches un alongside b anches o he bile duc s and cou se oge he h oughou he
li e pa enchyma wi hin pe ipo al a ea, which consis s o ou essels: hepa ic a e y, po al ein, bile duc ile and
lympha ic essel, o ming he po al a ea. The pe ipo al blood essels supply’s he li e pa enchyma by lowing h ough
he li e sinusoids o he cen al ein, which lies in in he cen e o he cen ilobula a ea.
The blood supply o he li e pa enchyma lows om he po al a ea o he cen al eins. Acco dingly, he hepa ic
pa enchyma o classical li e lobule is di ided in o 3 zones (Allison e al., 2022):
• Zone 1 o he pe ipo al (pe iphe al) a ea is closes o he a e ial and po al blood supply and hence bea s he
b un o all o ms o oxic inju y.
• Zone 2 is he in e media e midzonal a ea.
• Zone 3 o he cen ilobula a ea su ounds he cen al ein and is mos emo e om he blood supply and hus
su e s om he e ec s o hypoxic inju y.
The sinusoids a e lanked by hepa ocy es. Hepa ocy es a e he chie unc ional cells o he li e and pe o m an
as onishing numbe o me abolic, endoc ine and sec e o y unc ions. Roughly 80% o he mass o he li e is con ibu ed
by hepa ocy es. In h ee dimensions, hepa ocy es a e a anged in pla es ha anas omose wi h one ano he . The cells a e
polygonal in shape and hei sides can be in con ac ei he wi h sinusoids (sinusoidal ace) o neighbou ing hepa ocy es
(la e al aces). A po ion o he la e al aces o hepa ocy es is modi ied o o m bile canaliculi. Mic o illi a e p esen
abundan ly on he sinusoidal ace and p ojec spa sely in o bile canaliculi (Allison e al., 2022).
The li e is a diges i e gland and a key o gan which con ols many li e unc ions. I plays a p ominen ole in mammalian
physiology, bo h in anabolism (p o eins, lipids and ca bohyd a es), ca abolism (ni ogen, glycogenolysis, de oxi ica ion)
and i se es as a s o age si e o many subs ances mainly glycogen (Hin on and Lau en, 1990; Takashima and Hibiya
1995; Akiyoshi and Inoue, 2004). Con aminan s, such as hea y me als, pes icides, hyd oca bons and physico-chemical
wa e pa ame e s can al e he s uc u e and me abolism o he li e (B usle e al., 1996). His ological al e a ions
common in li e ollowing exposu es o oxican s include cloudy swelling, a ophy, hepa ocy e hype ophy, nec osis,
hype plasia, acoula degene a ion, a y degene a ion, conges ion and bile s agna ion (Takashima and Hibiya, 1995).
The heal h e ec s o oxic subs ances and haza dous was es a e no ye ully unde s ood. Resea ch o be e unde s and
how hese exposu es may impac heal h is ongoing. Meanwhile, e o s o educe exposu es con inue. Reducing
exposu e o oxic subs ances and haza dous was es is undamen al o en i onmen al heal h.
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2. Ma e ials and me hods
The s udy was a sub-ch onici y es ing o 14 days. Thi y (30) inb ed male Wis a a s we e ob ained om he animal
house o he Depa men o Ana omy, Facul y o Basic Medical Sciences, Uni e si y o Benin o his s udy. The a s we e
di ided in o expe imen al and con ol g oups:
• Con ol G oup: Fi e (5) a s we e used o his g oup. They we e un ea ed wi h a ge chemical (TC), and we e
only gi en only wa e and ood.
• Expe imen al G oup: Twen y- i e (25) a s we e used o he expe imen g oup. They we e ea ed wi h he
s udy TCs. This g oup was sub-di ided in o 5 Wis a a pe TC ea ed g oup o Cd, C , Cu, Ni and Pb.
In es ima ion o he a exposu e dose (RED) o he s udy, OEDC (2001) e e ence o al LD50 dose o Wis a Ra (in
mg/Kg o body weigh ) o he TCs – Cd (63mg/kg); C (46 mg/kg), Cu (481 mg/kg); Nickel (300 mg/kg) and Pb (600
mg/kg), was used as a guideline s anda d o he uppe limi s o dose adminis a ion (OECD, 2001). Ten imes (10x) he
TC concen a ion ha is abo e maximum allowable oxican concen a ion (MATC) o su ace esh wa e , bu below
he median le hal dose (LD50) e e ence concen a ion o Wis a Ra s was used as he guideline o es ima ion o he
RED (Hounkpa in e al., 2013; Think a ok, e al., 2014). Thus analy ical g ade me allic sal s o he TCs concen a ions
ha a e 10x >MATC s anda d pe TC, bu below he LD50 pe TC o Wis a Ra was dissol ed in 100li es o dis illed
wa e o make he s ock solu ion. 1ml o he s ock, o each o TCs, was adminis e ed o ally/day o 14 days o he es
a s (Think a ok, e al., 2014). The e o e, RED in mg/ml o his s udy was: Cd (0.0001 mg/ml), C (0.01 mg/ml), Cu(0.02
mg/ml), Ni(0.25 mg/ml) and Pb(10.0 mg/ml). O al ou e was chosen as he ou e o adminis a ion o he es solu ion
because i is he mos common mode o exposu e o he a ge oxican s (ATSDR, 2004; ATSDR, 2007; ATSDR, 2012a,
2012b).
All animals used in his s udy we e handled wi h ega ds o in e na ional, na u al and ins i u ional guidelines o ca e
and use o labo a o y animals in biomedical esea ch as p omulga ed by he Canadian Council o Animal Ca e (CCAC,
1984). S udy animals we e housed in cages wi h wi e ba lids used o hold wa e bo le and eeds o p e en
con amina ion wi h u ine o eces. Bedding was placed di ec ly in o he shoe box cage o allow he abso p ion o u ine.
Tes animals we e kep in well- en ila ed oom a ambien empe a u e o 28.0±2.0 oC unde 12hou ligh /da k cycle
well ed wi h ood and wa e ad libi um. Gene ally, he s udy was conduc ed in acco dance wi h he ecommenda ions
om he decla a ion o Helsinki on guiding p inciples in ca e and use o animals (Obianime and Robe s, 2009).
His ological issue p ocessing and quali a i e analysis o p epa ed issue slides was done a he His ology Labo a o y o
he Depa men o Ana omy, School o Basic Medical Sciences, Uni e si y o Benin. Resec ed a ge o gan o li e was
collec ed in ials illed wi h p ese a i e (10% neu ally-bu e ed o malin solu ion), and anspo ed o he Uni e si y
o Benin His ology labo a o y o issue p ocessing and s aining. The p epa ed issue slides we e used o quali y
his ological e alua ions. (D u y and Walling on, 1980; Allison and Paul, 2014; Allison and Paul, 2018)
3. Resul s
3.1. G oss Ana omical Assessmen
The Wis a a sub-ch onic oxici y showed ha , a s exposed o he daily a exposu e doses (RED) o Cu1, Ni1 and Pb1
died. Only hose exposed o he daily doses o Cd1, C 1 and con ol su i ed he 14day expe imen . Table 1 showed ha
he e was no signi ican di e ence (P> 0.05) when co ela ing weigh gain be ween he ea ed and con ol g oups.
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Table 1 co ela ing weigh gain be ween expe imen al and con ol g oups using es analysis
G oup
No o Male
Ra s
Daily RED
(mg/ml)
Exp.
Days
Mean Wo
(g)
mean W1
(g)
Weigh
Gain
Sig. (2-
ailed)
Con ol
Nil
14
175.5
208.4
32.9
0.300
No
Signi ican
Cd1
5
0.0001
14
180.6
212.3
31.7
0.419
No
Signi ican
C 1
5
0.01
14
175.3
203.6
28.3
0.215
No
Signi ican
Cu1
5
0.02
14
198.4
228.4
30.0
0.216
No
Signi ican
Ni1
5
0.025
14
201.0
230.4
29.4
0.650
No
Signi ican
Pb1
5
0.01
14
180.7
210.5
29.8
0.188
No
Signi ican
Key: TC = RED – Ra Exposu e Dose; Exp. = Expe imen ; W0 = Ini ial Weigh ; W1 = Final Weigh ; Cd1, C 1, Cu1, Pb1 and Ni1 = Hea y me al exposu e
concen a ion; Conc = Concen a ion; Sig: Signi icance; Mean alues (p<0.05) a e signi ican ly di e en
3.2. His ology
Pla e A-D a e obse ed mic og aphs o Li e o Wis a a s:
3.2.1. Pla e A: A mic og aph o he con ol Wis a a
• Diagnos ic Lesion: No mal A chi ec u e
• Diagnos ic No e: The li e mic og aph shows he cen ilobula a ea wi h no mal his ological a chi ec u e,
which consis s o o ganized lobule wi h a cen al ein, hepa ocy es a anged in co ds and capilla y sinusoids
unning be ween he ows o co d
3.2.2. Pla e B: A mic og aph o Wis a a exposed o Pb
• Diagnos ic Lesion: Hepa ocy e hype ophy wi h associa ed sinusoidal dila ion
• Diagnos ic No e: The li e mic og aph shows he pe ipo al a ea, which consis o di used hype ophied
hepa ocy es wi h mild sinusoidal dila ion. The hepa ocy es’cy oplasm is enla ged and pale wi h a g ound glass
appea ance. I is associa ed wi h sinusoidal dila ion – he sinusoidal spaces a e enla ged when compa ed wi h
he con ol mic og aph. O he obse ed his ological al e a ions include:
o Po al ein epi helial dis up ion: The epi helium o he po al ein is dis up ed esul ing in
ex a asa ion o blood in o he in e s i ium.
o Coagula i e nec osis: I is cha ac e ized by a eas o loss o hepa ocy es, wi h obse ed ka yolysis and
eplacemen wi h e y h ocy es
3.2.3. Pla e C: A mic og aph o he Wis a a exposed o Cd
• Diagnos ic Lesion: Mild hepa ocy es hyd opic degene a ion wi h associa ed coagula i e nec osis and
hepa ocy e hype ophy
• Diagnos ic No e: The li e mic og aph shows he pe ipo al a ea, which consis o mild hyd opic degene a ion
• hepa ocy es we e swelling and ounding up wi h wa e y oedema ous wispy a i ied cy oplasm ha is less
eosinophilic han he no mal cells. Some o he inju ed hepa ocy es a e unde going se e e o m o hyd opic
degene a ion (i.e. ballooning degene a ion) which is cha ac e ized by hei cy oplasm appea ing swollen and
g anula , which ends o condense a ound he nucleus. O he obse ed his ological al e a ions include:
o Coagula i e nec osis: I is cha ac e ized by a eas o loss o hepa ocy es, wi h obse ed ka yolysis and
eplacemen wi h e y h ocy es
o Hepa ocy e hype ophy: The a ec ed hepa ocy es cy oplasm ha e a pale, g ound glass appea ance
wi h associa ed ka yomegaly and mul inuclea ed hepa ocy es.
o D opou ballooning nec osis: A small clus e o degene a ing hepa ocy es show d opou ballooning
nec osis, which cha ac e ized by ka iolysis o hei nucleus.
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Figu e 1 Pho omic og aph (H and E) 400x
magni ica ion o no mal a chi ec u e o he li e o he
con ol wis a a showing hepa ocy es (H) Sinusoids
(S) cen al ein (CV) and bile duc (BD)
Figu e 2 Pho omic og aph (H and E) 400x
magni ica ion o li e exposed o pb showing he
pe ipo al a ea which consis o po al ein (PV) bile
duc ile, po al ein epi helial dis up ion (PVED)
coagula i e nec osis (CN) hype ophied hepa ocy es
(hh) and sinusoid dila ion (SD)
Figu e 3 Pho omic og aph (H and E) 400x magni ica ion
o li e exposed o Cd showing he Cen ilobula a ea
which consis o cen al ein (CV) coagula i e nec osis
(CN) hype ophied hepa ocy es (IR) d opou ballooning
(DB) and swelling o he hepa ocy e due o ballooning
Degene a ion (S-BD)
Figu e 4 Pho omic og aph (H and E) 400x
magni ica ion o li e exposed o c showing he
pe ipo al a ea which consis o he conges ed hepa ic
ein (CHP) bile duc ules (BD) cell in il a ion (IR)
swelling hepa ocy es wi h ballooning degene a ion (s-
DB)
3.2.4. Pla e D: A mic og aph o he Wis a a exposed o C
• Diagnos ic Lesion: Mode a e Hepa ocy es hyd opic degene a ion wi h associa ed in lamma ion
• Diagnos ic No e: The li e mic og aph shows he pe ipo al a ea, which consis o mode a e hyd opic
degene a ion – hepa ocy es we e swelling and ounding up wi h wa e y oedema ous wispy a i ied cy oplasm
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ha is less eosinophilic han he no mal cells. Some o he inju ed hepa ocy es a e unde going se e e o m o
hyd opic degene a ion (i.e. ballooning degene a ion) which is cha ac e ized by hei cy oplasm appea ing
swollen and g anula , which ends o condense a ound he nucleus. O he obse ed his ological al e a ion
include:
In lamma o y cells in il a ion: The e is p esence o mul iple oci o in lamma o y cells.
4. Discussion
4.1. G oss Assessmen
This in ol es he weigh ela ionship be ween he con ol and expe imen al g oup. The e was no signi ican di e ence
in mean weigh gain be ween expe imen al Wis a Ra s g oups exposed o TCs Ra Exposu e Doses (REDs) o Cd1, C 1,
Cu1, Ni1 and Pb1, and he con ol g oup. This implies ha he RED does no ha e signi ican e ec on he weigh o
Wis a a s, which is consis en wi h o he s udies in which Wis a Ra s we e exposed o hea y me als. (Melo e al.,
1998; Honglin e al., 2017).
4.2. His ology
The li e is he p ima y a ge o gan ollowing acu e o ch onic oxici y o exposu e. The up ake o hea y me als in o
he li e is c i ical o he de elopmen o o e all oxici y induced by hea y me als. App oxima ely hal o hea y me als
abso bed sys emically a e apidly accumula ed in he li e , which esul ed in he educed a ailabili y o hea y me als
o o he o gans like he kidneys, lungs and es es, which a e mo e sensi i e o i s oxic ac ions (DelRaso e al., 2003).
In his s udy, he li e showed a iable his ological al e a ions in he deg ee o li e cell inju y bu i was mos ma ked
in cen ilobula a ea (zone 3 o classical lobule) wi h mildly inju ed hepa ocy es, which appea swollen wi h g anula
cy oplasm ha ends o condense a ound he nucleus (S-BD - ballooning degene a ion). Obse ed diagnos ic lesions
include:
4.2.1. Hepa ocy e hype ophy
Hepa ocy e hype ophy is a o m o cy ologic al e a ion ha is diagnosed based on an obse able inc eased in size o
hepa ocy es compa ed wi h concu en con ol li e . I is mos eadily appa en when i has he commonly occu ing
cen ilobula dis ibu ion pa e n; when i is panlobula , compa ison wi h concu en con ols can p o ide diagnos ic
con i ma ion (NTP, 2014; Allison e al., 2022). When mild, de ec ion o hepa ocy e hype ophy may be di icul , bu i s
iden i ica ion is acili a ed a low magni ica ion. I mos equen ly a ec s cen ilobula hepa ocy es, depending upon
he xenobio ic and he dose adminis e ed, al hough he hype ophy can ex end in o he middle o he hepa ic lobule o
become panlobula . I is also possible o pe ipo al hepa ocy es o be p ima ily a ec ed, hough ca e mus be aken no
o con use pe ipo al hype ophy wi h p ocesses ha esul in sh inkage o cen ilobula hepa ocy es (e.g., glycogen
deple ion) (NTP, 2014; Allison e al., 2022). In his s udy, hype ophic hepa ocy e cy oplasm was pale wi h g ound
glass appea ance and associa ed wi h ka yomegaly and mul inuclea ed hepa ocy es. This was consis en wi h ch onic
exposu e o Wis a a li e o some non-geno oxic hepa ic oxican s. (NTP, 2014).
4.2.2. Hepa ocy es hyd opic degene a ion
Hyd opic degene a ion o hepa ocy es desc ibes he swelling and ounding up o inju ed hepa ocy e which is
conside ed as a sign o p og ession o cell dea h. The inju ed cells p esen a clea ield in cy oplasm which a e spaces
o accumula ing massi e glycogen (NTP, 2014; Allison e al., 2022). G anules a e o med a ound he nuclei which a e
con e gence o mi ochond ia, endoplasm e iculum and o he o ganelles (NTP, 2014; Allison e al., 2022). In his s udy.
mild and mode a e hepa ocy eshyd opic degene a ion was seen in pla es C and D espec i ely. The hepa ocy es we e
swelling and ounding up wi h wa e y oedema ous wispy a i ied cy oplasm ha is less eosinophilic han he no mal
cells. This is consis en wi h s udies o a s exposed o xenobio ics (NTP, 2012; NTP, 2014)
4.2.3. Ballooning Degene a ion
Is a se e e o m o hyd opic degene a ion. I esul s in deple ion o adenosine iphospha e (ATP) and ise in
in acellula calcium, leading o loss o plasma memb ane olume con ol and dis up ion o he hepa ocy e in e media e
ilamen ne wo k (NTP, 2014; Allison e al., 2022). Mic oscopically i can be iden i ied a low powe as hepa ocy es 2 -
3 imes he size o no mal adjacen hepa ocy es. Ballooned cells lose hei usual polygonal shape and become ounded
wi h wa e y oedema ous wispy a i ied cy oplasm ha is less eosinophilic han he neighbo ing cells wi h acuoliza ion
and lacking a accumula ion (NTP, 2014; Allison e al., 2022). These cells usually demons a e clumping o in e media e
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ilamen s, cha ac e ized as s ands o eosinophilic, opey cy oplasmic ma e ial e e ed o as Mallo y bodies. In his
s udy, ballooning dege ma ion was seen in pla es C and D. I is cha ac e ized by hei cy oplasm appea ing swollen and
g anula , which ends o condense a ound he nucleus. This was consis en wi h oxicological s udies ca ied ou by
NTP, 2014.
4.2.4. Sinusoidal dila ion (SD)
Hepa ic sinusoidal dila ion e e s o he enla gemen o he hepa ic a e y. I usually occu s in in cen ilobula a ea, o
less equen ly a pe ipo al. Th ee pa homechanisms ha e been p oposed (NTP, 2014; Allison e al., 2022):
A ophy o he hepa ic co ds as a p ima y e en .
Hemodynamic ac o s emodeling he sinusoidal lumen: Inc eased hepa ic a e ial blood low (e.g. a e io enous
mal o ma ions) could cause dila ion o sinusoids, ele an in po al ein blood low dep i a ion. Localized obs uc ion
o sinusoids may also induce ups eam SD, ele an in pe isinusoidal ib osis, nodula egene a i e hype plasia, o SOS
(oxalipla in-associa ed SD).
Implica ion o soluble sys emic ac o s including IL-6 and ascula endo helial g ow h ac o (VEGF), ele an in SIRS-
associa ed SD. Ac i a ion o neu ogenic locus no ch homolog p o ein 1 (No ch 1) pa hway (signaling ha helps
de e mine he specializa ion o cells in o ce ain cell ypes ha pe o m pa icula unc ions in he body – cell a e
de e mina ion) in sinusoidal endo helial cells could also induce SD (Ma zano e al., 2015).
In his s udy, he sinusoidal dila ion was di use and mainly a ound he pe ipo al a eas. This was consis en wi h he
his ological indings in he li e o a xenobio ic exposed a (Ma zano e al., 2015)
4.2.5. O he obse ed his ological al e a ions
Coagula i e nec osis (o acidophilic degene a ion) also occu ed in his s udy. I is cha ac e ized by he cy oplasm
becoming in ensely eosinophilic, he nuclei a e small and pykno ic and wi h an e en ual ex usion om he cell, lea ing
behind nec o ic, acidophilic mass called councilman body o acidophil body. Lesions also consis o ano he ype o
hepa ocellula nec osis known as D opou Ballooning (DB) nec osis in which isola ed o small clus e s o hepa ocy es
unde go lysis. The e is also In lamma o y Response (IR), which is in il a ion by mononuclea in lamma o y cells,
usually in he po al ac s, bu may pe mea e in o he lobules. Findings in his s udy we e consis en wi h o he s udies:
Mohapa a e al. (2013) showed ha his opa hological al e a ions in he li e issue o hea y me als ea ed mice
mani es ed by dis up ion o hepa ocy ic pla es, disin eg a ion o hepa ocy es ma ked by up u e o cell memb ane,
cy oplasmic acuoliza ion and pyknosis o nuclei. El-Re aiy (2013) showed se e e hepa ic nec osis, a y changes,
degene a ion signs and in lamma o y cell in il a ions o hea y me als adminis a ed a s. The s udy concluded ha , he
his opa hological changes o he li e ea ed wi h hea y me als migh be due o he o ma ion o highly eac i e adicals
and subsequen lipid pe oxida ion. The accumula ed hyd ope oxidase can cause hepa oxici y, which is associa ed wi h
he pe oxida ion o memb ane phospholipids by lipid hyd ope oxidase, he basis o hepa ocellula damage
(Renugade i, 2010). Jihen e al. (2008) also suppo ed he a o emen ioned pa hogenesis by sugges ing ha Cd inhibi s
p o ein syn hesis and glycogen me abolism in li e o hea y me als con amina ed a s. Some o he esul s also showed
cellula in il a ion and hemo hagic spo s o hea y me als ea ed a li e also ound in ag eemen wi h acu e and
ch onic e ec s o Cd documen ed by (Mohapa a e al., 2013). Oma , (2013) has also epo ed ela i ely hemo hage in
li e o hea y me al ea ed Wis a a s. I was sugges ed o be due o he conges ion o he blood essels and blood
sinusoids h ough which blood has escaped. Mo eo e , some schola s epo ed ha a conside able numbe o Kup e
cells a e obse ed in he sinusoid walls a e hea y me al ea men o Wis a a s. P oli e a ion and inc eased numbe
o Kup e cells could indica e de ense mechanism agains hea y me als oxici y (Oma , 2013) and (ElRe aiy, 2013).
5. Conclusion
This s udy was ecologically ele an . I was able o demons a e ha known con aminan s o oil spill si es, i consumed
a a es equal o o highe han hei o al e e ence dose o mammalian species can cause li e diso de s, e en a sub-
ch onic oxici y pe iod. The s udy has once mo e gi en c edence o he use o his ology as a bioma ke o assess
suble hal le el o en i onmen al s esso s, and in de e mina ion and ex apola ion o he ecosys em pollu ion
capabili ies o he exposu e o he s udied a ge chemicals.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 26(02), 2590-2598
2597
Compliance wi h e hical s anda ds
Acknowledgmen s
We wish o hank he Depa men o Ana omy, Uni e si y o Benin, Nige ia o he use o hei Ana omy House o his
s udy.
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
S a emen o e hical app o al
I s udies in ol e use o animal/human subjec , au ho s mus gi e app op ia e s a emen o e hical app o al. I no
applicable hen men ion ‘The p esen esea ch wo k does no con ain any s udies pe o med on animals/humans
subjec s by any o he au ho s’.
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